FREE VIRIONS GENERATED CAN THEN INFECT NEIGHBORING HOST

SEROLOGY AND MOLECULAR DETECTION OF VIRAL INFECTIONS CELLS AND BEGIN NEW REPLICATION CYCLES THAT PROMOTE
DISSEMINATION OF THE INFECTION.

VIRUSES IMMUNE DEFENSES AGAINST VIRAL INFECTIONS

● OBLIGATE INTRACELLULAR PATHOGENS THAT RELY ON THE INNATE IMMUNITY
HOST CELL FOR THEIR REPLICATION AND SURVIVAL ● NATURALLY OCCURRING BARRIERS AS FIRST LINE OF DEFENSE
● CONSISTS OF A CORE OF DNA OR RNA PACKAGED INTO A (SKIN AND MUCOUS MEMBRANE)
PROTEIN COAT OR CAPSID ● IF INVASION IS SUCCESSFUL, OTHER INNATE DEFENSES ARE
● FOR SOME VIRUSES, CAPSID IS SURROUNDED BY AN OUTER ACTIVATED WHEN CELLS OF THE IMMUNE SYSTEM RECOGNIZE
ENVELOPE OF GLYCOLIPIDS AND PROTEINS DERIVED FROM PAMPS OF OR WITHIN VIRUS-INFECTED CELLS.
THE HOST CELL MEMBRANE. ● TWO NONSPECIFIC DEFENSES:
● SIZE IS MEASURED IN NANOMETERS. ○ 1. TYPE 1 INTERFERONS
○ 2. NATURAL KILLER CELLS
● IFN-A AND IFN-B ARE PRODUCED BY VIRUS-INFECTED CELLS.
● ACTIONS:
○ 1. INHIBIT VIRAL REPLICATION
■ BY INDUCING THE TRANSCRIPTION OF
SEVERAL GENES THAT CODE FOR PROTEINS
WITH ANTIVIRAL ACTIVITY.
○ 2. ENHANCE THE ACTIVITY OF NK CELLS, WHICH BIND
TO VIRUS-INFECTED CELLS AND RELEASE CYTOTOXIC
PROTEINS /(PERFORIN & GRANZYMES)
● CELLS DIE AND RELEASE THE VIRUS.
● CELL-FREE VIRIONS ARE NOW
● ACCESSIBLE TO ANTIBODY MOLECULES.
● IF INNATE DEFENSES ARE INSUFFICIENT, SPECIFIC HUMORAL
AND CELL-MEDIATED DEFENSES ARE ACTIVATED
VIRUS-SPECIFIC
● VIRUS-SPECIFIC ANTIBODIES ARE PRODUCED BY B CELLS
AND PLASMA CELLS.
● NEUTRALIZATION (PRODUCTION OF ANTIBODIES THAT ARE
SPECIFIC FOR A COMPONENT OF THE VIRUS THAT BINDS TO A
RECEPTOR ON THE HOST CELL MEMBRANE)
● NEUTRALIZING ANTIBODIES PREVENT VIRUS FROM
ATTACHING TO AND PENETRATING THE HOST CELL.
● SECRETORY IGG ANTIBODIES - NEUTRALIZE VIRUSES IN THE
MUCOSAL SURFACE.
● IGM AND IGG ANTIBODIES - BIND TO VIRUSES IN THE
BLOODSTREAM AND INHIBIT DISSEMINATION OF THE
INFECTIONS
CELL-MEDIATED IMMUNITY
● ANTIBODIES CANNOT REACH VIRUSES THAT HAVE ALREADY
PENETRATED HOST CELLS.
● LEADED BY:
○ TYPE 1 HELPER (TH1) CELLS
○ CYTOTOXIC T LYMPHOCYTES (CTL)
● THI CELLS PRODUCE INTERFERON-GAMMA AND IL-2.
 ● IL-2 ASSISTS IN THE DEVELOPMENT OF CTL ● PROGRESSION
● CD8, AND COSTIMULATORY MOLECULES B7 AND CD28 ● LIVER ENLARGEMENT (HEPATOMEGALY) AND TENDERNESS,
INTERACT. JAUNDICE, DARK URINE, AND LIGHT FECES.
● STIMULATE THE GRANULE IN CTL TO RELEASE PERFORIN & ● INITIAL LAB FINDINGS:
GRANZYMES. ○ ELEVATION IN BILIRUBIN AND ALT
● ACTIVATE APOPTOSIS IN THE HOST CELL. ○ NON-SPECIFIC INDICATORS OF LIVER INFLAMMATION.

VIRAL ESCAPE MECHANISMS HEPATITIS A

1. VIRUSES ARE RAPIDLY DIVIDING AGENTS CAPABLE OF ● NONENVELOPED, SINGLE-STRANDED RIBONUCLEIC ACID
FREQUENT GENETIC MUTATIONS. (PRODUCTION OF NEW (RNA) VIRUS THAT BELONGS TO THE HEPATOVIRUS GENUS OF
VIRAL ANTIGENS) THE PICORNAVIRIDAE FAMILY.
2. SOME VIRUSES CAN ESCAPE THE ACTION OF COMPONENTS ● TRANSMITTED PRIMARILY BY THE 1. FECAL-ORAL ROUTE, 2.
OF THE INNATE IMMUNE SYSTEM SUCH AS INTERFERONS, CLOSE PERSON-TO-PERSON CONTACT, OR 3. INGESTION OF
COMPLEMENT PROTEIN, OR LYSOSOMAL ENZYMES. CONTAMINATED FOOD OR WATER
3. VIRUSES CAN EVADE THE HOST'S DEFENSE BY SUPPRESSING ● AFTER INCUBATION OF 28 DAYS, IT PRODUCES SYMPTOMS OF
THE ADAPTIVE IMMUNE SYSTEM. ACUTE HEPATITIS IN ADULTS; SYMPTOMS IN CHILDREN ARE
4. SOME VIRUSES CAN REMAIN IN LATENT STATE. ASYMPTOMATIC.
● DOES NOT PROGRESS TO CHRONIC: SELF-LIMITING;
LABORATORY TESTING FOR VIRAL INFECTION SYMPTOMS RESOLVE W/IN 2 MONTHS.
SEROLOGICAL TESTS
● IMPORTANT IN MONITORING THE COURSE OF INFECTION,
DETECTING PAST INFECTIONS, AND ASSESSING IMMUNE
STATUS
MOLECULAR TESTS
● ENHANCED OUR ABILITY TO DETECT ACTIVE INFECTION AND
ESSENTIAL IN GUIDING ANTIVIRAL THERAPY
● IGM ANTIBODIES INDICATES A CURRENT OR RECENT VIRAL
INFECTION.
● IGG ANTIBODIES SIGNIFY EITHER A CURRENT OR PAST
INFECTION AND, IN MANY CASES, IMMUNITY. ● HAV ANTIGENS - SHED IN THE FECES OF INFEC. INDIV. DURING
● IGM ANTIBODY IN NEWBORN'S SERUM - CONGENITAL ACUTE STAGE; DECLINE TO LOW LEVEL; NOT CLINICALLY
INFECTION USEFUL INDICATOR OF DSE.
● IGG ANTIBODY IN INFANT'S SERUM - MATERNAL ANTIBODIES ● SEROLOGICAL TEST FOR ANTIBODY (AUTOMATED,
THAT CROSSED THE PLACENTA CHEMILUMINESCENT MICROPARTICLE IMMUNOASSAYS)
● IGM ANTI-HAV - PRIMARY MARKER TO DETECT ACUTE HEPA.
HEPATITIS VIRUSES A; DETECTABLE AT THE ONSET OF SYMPTOMS (DECLINES
● HEPATITIS MEANS INFLAMMATION OF THE LIVER WITHIN 6 MOS.)
● IT CAN BE CAUSED BY VIRUSES AND NON-INFECTIOUS ● POSITIVE TOTAL ANTI-HAV ANTIBODIES, NEGATIVE IGM
AGENTS (IONIZING RADIATION, CHEMICALS, AND AUTOIMMUNE ANTI-HAV - PX HAS DEVELOPED IMMUNITY TO THE VIRUS
PROCESSES) MOLECULAR METHOD
● PRIMARY HEPATITIS VIRUSES AFFECT MAINLY THE LIVER. ● MOLECULAR METHOD (HAV RNA) PROVIDES MORE
● HEPATITIS A VIRUS (HAV) AND HEPATITIS E VIRUS (HEV) - SENSITIVITY
FECAL-ORAL ROUTE ● RT PCR (REVERSE TRANSCRIPTASE - PCR)
● HEPATITIS B VIRUS (HBV), HEPATITIS C VIRUS (HCV) & ● VACCINE (CONTAINING FORMALIN-KILLED HAV WAS LICENSED
HEPATITIS D VIRUS (HDV) - PARENTERAL ROUTE IN MID- 1990S.
EARLY OR ACUTE STAGE ● PREFERRED TREATMENT FOR PERSONS AGED 1-40 YEARS
● GENERAL FLU-LIKE SYMPTOMS, MILD TO MODERATE PAIN IN ● IM INJECTION OF IMMUNE GLOBULIN (ANTIBODIES TO HAV)
RIGHT UPPER QUADRANT (RUQ) OF THE ABDOMEN. ● IN INDIV. OF ANY AGE.
● TREATMENTS MUST BE ADMINISTERED WITHIN 2 WEEKS OF ● CONSISTS OF GENETICALLY MODIFIED VIRUS LIKE PARTICLES
EXPOSURE EXPRESSING A GENE THAT CODES FOR A KEY HEV PROTEIN.

HEPATITIS E
● NONENVELOPED, SINGLE-STRANDED RNA VIRUS THAT
BELONGS TO THE GENUS HEPEVIRUS, IN THE FAMILY
HEPEVIRIDAE
● A MAJOR CAUSE OF HEPATITIS WORLDWIDE
● TRANSMITTED PRIMARILY BY THE FECAL-ORAL ROUTE;
HOWEVER, PERSON-TO-PERSON TRANSMISSION IS
UNCOMMON; CAN BE TRANSMITTED THROUGH BLOOD ● SEROLOGIC TESTING FOR ANTIBODY (EI ASSAYS THAT USE
TRANSFUSIONS SYNTHETIC AND RECOMBINANT HEV
● FOUR GENOTYPES: ● ANTIGENS & RAPID IMMUNOCHROMATOGRAPHIC ASSAY)
a. GENOTYPES 1 AND 2 - ASSOCIATED WITH ● IT CAN DETECT ALL FOUR GENOTYPES OF THE VIRUS.
CONSUMPTION OF FECALLY-CONTAMINATED ● IGM ANTI-HEV - ACUTE INFECTION; ELEVATED FOR 8 WEEKS;
DRINKING WATER IN DEVELOPING REGIONS OF THE UNDETECTABLE BY 32 WEEKS.
WORLD WITH POOR SANITATION (PARTS OF AFRICA, ● IGG ANTI-HEV - APPEAR SOON AFTER IGM; REACH PEAK
ASIA, THE MIDDLE EAST, AND MEXICO) LEVEL ABOUT 4 WEEKS; PERSISTS FOR SEVERAL YEARS
b. GENOTYPES 3 AND 4 - ZOONOTIC INFECTION ● MOLECULAR TESTING FOR HEV RNA (RECOMMENDED FOR
(CONSUMPTION OF INFECTED PORK AND POSSIBLY BY IMMUNOCOMPROMISED PERSONS)
DIRECT CONTACT WITH INFECTED ANIMALS OR ● PERFORMED BY REAL-TIME PCR OR LAMP (LOOP-MEDIATED
FECALLY-CONTAMINATED WATER): DEVELOPED PARTS ISOTHERMAL AMPLIFICATION ASSAY)
OF THE WORLD, INCLUDING EUROPE, NORTH ● CAN BE PERFORMED ON BLOOD (UNDETECTABLE ABOUT 3
AMERICA, AND JAPAN WEEKS AFTER SYMP. ONSET) OR STOOL SAMPLES
(UNDETECTABLE AT ABOUT 5 WEEKS)

HEPATITIS B
● DNA VIRUS BELONGING TO THE HEPADNAVIRIDAE FAMILY
● MAJOR CAUSE OF MORBIDITY AND MORTALTY THROUGHOUT
THE WORLD
● HIGHLY ENDEMIC IN THE FAR EAST, PARTS OF THE MIDDLE
EAST, SUB-SAHARAN AFRICA, AND THE AMAZON AREAS
● TRANSMITED THROUGH PARENTERAL ROUTE (INTIMATE
CONTACT WITH HBV-CONTAMINATED BLOOD OR OTHER BODY
FLUIDS - SEMEN, VAGINAL SECRETIONS, AND SALIVA)
● MAY ALSO OCCUR VIA PERINATAL ROUTE (FROM INFECTED
MOTHER TO INFANT, MOST LIKELY DURING DELVERY)
● ACUTE HEPATITIS INDISTINGUISHABLE FROM OTHER TYPES ● VACCINE CONTAINING RECOMBINANT HEPATITIS B SURFACE
OF HEPA. ANTIGEN (HBSAG)
● INCUBATION PERIOD OF 2 TO 6 WEEKS; SELF-LIMITING; ● MOST WIDELY USED VACCINE IN THE WORLD
RECOVERY OCCURRING BY 4 TO 6 WEEKS. ● HBIG (HEPATITIS B IMMUNE GLOBULIN)
● SOME PATIENTS MAY EXPERIENCE EXTRAHEPATIC SYMPTOMS o WTH HIGH CONC. OF ANTIBODIES TO HBV: FOR
(NEUROLOGICAL SYNDROMES, RENAL INJURY, PANCREATITIS, TEMPORARY PROTECTION)
AND HEMATOLOGIC ABNORMALITIES) ● INCUBATION PERIOD OF 30 TO 180 DAYS: SYMPTOMS MAY
● VACCINE HAS BEEN LICENSED FOR USE IN PEOPLE'S LAST SEVERAL WEEKS TO SEVERAL MONTHS
REPUBLIC OF CHINA.
● RECOVERY WITHIN 6 MONTHS THEN, DEVELOPS IMMUNITY.
 ● CHRONIC HBV INFECTION - VIRUS PERSISTS FOR 6 MONTHS
OR MORE
● MOST LIKELY TO DEVELOP IN IMMUNOSUPPRESSED, OR
THOSE WITH HIV.
● CHRONIC INFECTION WITH THE VIRUS RESULTS IN
INFLAMMATION AND DAMAGE TO THE LIVER AND PLACES THE
PATIENT AT INCREASED RISK OF DEVELOPING CIRRHOSIS OR
HEPATO CELLULAR CARCINOMA.
Symptoms
1. Dark urine
2. Joint and muscle pain
3. Fatigue
4. Fever
5. Loss of appetite
6. Weakness
7. Abdominal pain
8. Yellowing of the whites of the eyes and skin (jaundice)
● EIGHT GENOTYPES (DESIGNATED: THROUGH H) IDENTIFIED
BASEDI ON NUCLEOTIDE SEQUEND DIFFERENCES THEIR
GENOM
● 42 NM SPHERE CONSISTING OF A NUCCLOCAPSID CORE
SURROUNDED BY AN OUTER ENVELOPE OF LIPOPROTEIN ● ANTIBODIES APPEAR
● CORE OF THE VIRUS CONTAINS: CIRCULAR, PARTIALLY ● IGM ANTI-HBC (IOM ANTBODY TO TU CORL ANTIGEN) FIRST
DOUBLE-STRANDED DNA, A DNA DEPENDENT DNA ANTIBODY TO APPEAR
POLYMERASE ENZYME: AND TWO PROTEINS, HEPATITIS B ● (CURRENT OR RECENT INFECTION, APPEARS 1 TO 2 WEEKS
CORE ANTIGEN AND HEPATITIS BE ANTIGEN (HBEAG) AFTER HBSAG):
● OUTER ENVE. OF THE VIRUS: HEPATITIS B SURFACE ANTIGEN ● HELPFUL IN CASES WHICH HIBSAG IS UNDECTABLE
(HBSAG)
SEROLOGIC MARKERS 1. "CORE WINDOW" PERIOD (JUST BEFORE THE
● HBSAG – FIRST MARKER TO APPEAR DETECTABLE WTIN 2-10 APPEARANCE OF ANTIBODIES TO AG)
AFTER EXPOSURE 2. IN NEONATAL INFECTIONS
o (INDICATOR OF ACTIVE INFECTION; MARKER IN 3. INCASE OF FULMDNANT HEPATITIS
DETECTING INITIAL INFECTION) 4. IN ADITION NO HBSAG IN SORBENING BLOOD DONORS
● HBEAG - APPEARS SHORTLY AFTER TIBSAG DISAPPEARS
SHORTLY BEFORE HIBSAG IN ● IGG ANTI-HBE (IGG ANTIBODY TO THE CORE ANTIGEN)
o RECOVERING PATIENTS. PERSISTS FOR LIFETIME
o PRESENT DURING PERIODS OF ACTIVE o (INDICATE A PAST HBV INFECTION)
o REPLICATION OF VIRUS MOLECULAR METHODS
o (INDICATES HIGH DEGREE OF INFECTIVITY) ● HAVE BBEN DEVELOPED TO DETECT HBV DNA
● TRADITIONAL OR REAL-TIME POR OR BRANCHED DNA (BONA)
SIGNAL AMPLIFICATION
 1. HBV DNA IS PRESENT 21 DAYS BEFORE HBSAG (1 ● DETECTION OF HDV ANTIBODIES AND. HD RNA - MUST-BE
USEFUL ADJUNCT IN DETECTING EARLY ACUTE HBV PERFORMED IN HBSAG + PXD
INFECTION) ● IGG ANTI-HDY- INDICATES EXPOSURE TO THE VIRUS; ACUTE,
2. EVALUATE THE EFFECTIVENESS OF ANTIVIRAL CHRONIC, OR PAST
THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B ● HEPATITIS D INFECTION
● IGM ANTI-HD - PRODUCED DURING ACUTE HEPA D INFECTION
HEPATITIS D (PERSISTS FOR SHORT PERIOD OF TIME; PERSIST DURING
● DELTA HEPATITIS CHRONIC INFECTION)
● CONSISTS OF CIRCULAR RNA GINOM. AND.A SINGUE ● PATIENTS WITH CO-INFECTION HDY ANTIRODIES GM
SPRUOTURAIS PROTEIN CAUSED HEPATITIS DELTA ANTIGEN ANTI-HBC)
WITHIN ITS CORE, SURROUNDED В'A VIRAI ENVELORE THATS ● HDV RNA – present in all types of active HEPA D infection
OF HBV ORIGIN AND CONTAINS THE HBSAG; ● CONFIRMS + HDV ANTIBODY SCREEN PERFORMED by sensitive
● MEMBER OF THE DELTAVIRUS GENUS HAS real-time PT-PCR assays.
● EIGHT KNOWN HDV GENOTYPES
● PARENTERALLY-TRANSMITTED INFECTION THAT CAN OCCUR HEPATITIS C
ONLY IN THE PRESENCE OF HEPATITIS B ● ENVELOPED, SINGLE STRANDED POSTLIVE SENSE RNA VIRUS
● HIGHLY PREVALENT IN MEDITERRANEAN EUROPE, THE ● HEADACHE TO THE FAMILY FLAVIVIRIDAE AND THE GENUS
MIDDLE EAS, THE AMAZON BASIN; CENTRAL AFRICA, AND HEPACIVIRUS
PARTS OF ASIA ● MOST FREQUENT CAUSE OF CHRONIC LIVER INFECTION
CAN BE TRANSMITTED THROUGH: ● PREVIOUSLY “NON-A, NON-B INFECTIONS"
1. SEXUALLY IN SEMEN OR VAGINAL SECRETIONS; ● HAS SEVEN DIFFERENT GENOTYPES
2. BLOOD BY INTRAVENOUS DRUG USE, NEEDLESTICK INJURIES, ● TRANSMITTED MAINLY BY EXPOSURE TO CONTAMINATED
OR TRANSFUSIONS; BLOOD (IV DRUG USE: MAIN); ALSO, BY PERINATAL
3. OR PERINATALLY FROM MOTHER TO INFANT TRANSMISSION (6%)
● AVE. INCUBATION PERIOD OF 7 WEEKS
TRANSMITTED IN TWO WAYS. ● MAJORITY OF INFECTION ARE ASYMPTOMATIC.
1. CAN BE TRANSMITTED SIMULTANEOUSLY AS A CO-INFECTION
● CHRONIC HC INFECTION DEVELOP CIRRHOSIS, LATER
WITH HBV
HEPATOCELLULAR CARCINOMA
2. CAN BE CONTRACTED AS A SUPERINFECTION OF INDIVIDUALS
● ENVELOPED, SINGLE STRANDED POSITIVE SENSE RNA
WHO ARE ALREADY CHRONIC HBV CARRIERS
● HEADACHE
MOLECULAR TESTS
MOLECULAR TESTS FOR HCV RNA
● RNA
● USED TO MONITOR THE AMOUNT OF HOV RNA;
● LARGE, COMPLEX DNA VIRUSES OR HERPESVIRIDAD FAMILY
THAT ARE SURROUNDED BY A PROTEIN CAPSID AN
AMORPHOUS TECUMENT; AND AN OUTER ENVELOPE
● CAPABLE OF ESTABLISHING A LATENT INFECTION WITH
LIFELONG PERSISTENCE IN THE HOST INCLUDES EIGHT
VIRUSES (HERPES SIMPLEX VIRUSES (HSV 1 AND HSV-2), VZV,
EBV, CMV, AND THE HUMAN HERPES VIRUSES HHY-6, HHV-7,
AND HHV-8)
1. QUANTITATIVE
● PRESENCE OR ABSENCES OF HCV RNA ● HETEROPHILE ANTIBODIES AND AUTOANTIBODIES SUCH AS
● USED TO CONFIRM INFECTION IN HCV ANTIBOBDY - POSITIVE COLD AGGLUTININS, RHEUMATOID FACTOR, AND
PATIENTS ANTINUCLEAR ANTIBODIES
● DETECTION INFECTION IN ANTIBODY-NEGATIVE PATIENTS ● EARLY ANTIGENS (EAS) - ANTIGENS PRO DURING THE INITIAL
WHO ARE SUSPECTED OF HAVING HCV STAGES OF VIRAI REPLICATION IN THE LYTIC CYCLE
● SCREEN BLOOD AND ORGAN DONORS FOR HCV \ ● CLASSIFIED INTO TWO GROUPS
● DETECT PERINATAL INFECTIONS IN BABIES BORN TO ● EA-D - HAS A DIFFUSE DISTRIBUTION IN THE NUCLEUS AND
HCV-POSITIVE MOTHERS CYTOPLASM
● QUALITATIVE RT-PCR AND TRANSCRIPTION-MEDIATED ● EA-R-IS RESTRICTED TO THE CYTOPLASM ONLY
2. QUANTITATIVE ● LATE ANTIGENS OF EBV APPEAR DURING THE PERIOD OF THE
● USED TO MONITOR THE AMOUNT OF HCV RNA OR “VIRAL LYTIC CYCLE FOLLOWING VIRAL DNA SYNTHESIS
LOAD”, CARRIED BY PATIENTS BEFORE, DURING, AND AFTER ● VIRAL CAPSID ANTIGENS (VCAS) - PROTEIN CAPSID
ANTIVIRAL THERAPHY IN CHRONICALLY INFECTED ● MEMBRANE ANTIGENS - VIRAL ENVELOPE
INDIVIDUALS DETECT INFECTION IN ANTIBODY-NEGATIVE ● MONOSPOT
PATIENTS o DISTINGUISH THE HETEROPHILE ANTIBODY OF IM
● PERFORMED BY RT-PCR, REAL TIME PCR, OR BDNA FROM HETEROPHILE ANTIBODIES PRODUCED IN
AMPLIFICATION OTHER DISEASES
● SERUM PREMIXED WITH GUINEA PIG KIDNEY ANTIGEN WAS
EPSTEIN-BARR VIRUS STILL CAPABLE OF AGGLUTINATING HORSE RBCS, WHEREAS
● CAUSE: WIDE SPECTRUM OR DISEASES INFECTIOUS SERUM PREMIXED WITH BEEF ERYTHROCYTE ANTIGEN
MONONUCE BOSIS LYMPHOPROLIRERATIVE DISORDERS AND COULD NOT AGGLUTINATE HORSE RBCS BECAUSE THE
SEVERAL MALIGNANCIES HETEROPHILE ANTIBODY WAS ABSORBED DURING THE FIRST
● TRANSMISSION IS THRU INTIMATE CONTACT WITH SALIVARY STEP
SECRETIONS FROM AN INFECTED INDIVIDUAL ● NOT AS SENSITIVE OR SPECIFIC AS TESTS FOR ANTIBODIES
● OTHER MEANS OF TRANSMISSION (LESS FREQUENT): BLOOD TO EBV
TRANSFUSIONS, BONE MARROW AND SOLID ORGAN ● IF (-) FOR HITEROPHILE AB SCREEN, TEST FOR EBV SPECIFIC
TRANSPLANTS, SEXUAL CONTACT, AND PERINATAL EXPOSURE ANTIBODIES.
● OROPHARYNX - WHERE EBV INFECTION INITIALLY OCCUR ● TESTED THRU:
● VIRUS PRIMARILY INFECTS EPITHELIAI CELES AND B o INDIRECT IMMUNOFLUORESCENCE ASSAYS (IFA)
LYMPHOCY TES o ELISA/CLIA
● EBV BINDS TO B1 INTEGRINS ON SURFACE OF EPITHELIAL o FLOW CYTOMETRIC MICROBEAD IA
CELLS (ENDOCYTOSIS) ● IFA TESTS – “GOLD STANDARD” OR EBV SEROLOGY METHODS
● EBV ENTERS A LYTIC CYCLE ● IGM ANTI-VCA/ANTI-EA-D
● VIRAL REPLICATION, LYSIS OF HOST CELLS, AND RELEASE OF o ABSENCE OF ANTI-EBNA
INFECTIOUS VIRIONS o MOST USEFUL MARKER FOR ACUTE IM; ONSET OF
● VIRIONS SPREAD TO ADJACENT STRUCTURES: CLIN. SYMPTOMS
● SALIVARY GLANDS AND TONSILS ● IGG ANTI-VCA - ONSET OF IM BUT PERSISTS FOR LIFE/PAST
● EBV INFECTS B LYMPHOCYTES (LYMPHORETICULAR SYSTEM) INFECTION
● EBV ENTERS THE B CELLS BY BINDING TO SURFACE CD21 ● SOME INDIVIDUALS DEVELOP CHRONIC ACTIVE EBV
● VIRUS-INFECTED B CELLS SECRETE EBV SPECIFIC INFECTION WITH SEVERE, OFTEN LIFE-THREATENING
ANTIBODIES IM-ASSOCIATED SYMPTOMS THAT PERSIST OR RECUR FOR
MORE THAN 6 MONTHS AFTER THE ACUTE ILLNESS
● BEEN ASSOCIATED WITH SEVERE MALIGNANCIES
● HEMATOLOGIC (BURKITT'S LYMPHOMA AND HODGKIN ISOLATION
DISEASE) ● ISOLATION OF VIRUS IN CULTURE (TRADIONAL)
● NONHEMATOLOGIC (NASOPHARYNGEAL CARCINOMA AND ● HUMAN FIBROBLAST CELL LINES ARE INOCULATED WITH CMV
GASTRIC CARCINOMA) INFECTED SPECIMENS (URINE, RESPIRATORY SECRETIONS,
● LYMPHOPROLIVERATIVE DISORDERS: OR ANTICOAGULATED WHOLE BLOOD)
o CONTRAL NERVOUS SYSTEM (CNS) LYMPHOMAS IN ● PRESENCE OF VIRUS - CYTOPATHIC EFFECTS (CPE) THAT
PATIENTS WITH AIDS PRODUCE ENLARGED ROUNDED, REFRACTILE CELLS
o X-LINKED LYMPHOPROLIF ERATIVE DISEASE IN MALES ● CMN ANTIGENEMIA ASSAY- MOST WIDELY USED
WITH A RARE GENETIC MUTATION ● IMMUNOCY TOCHEMICAL/IMMUNOFLUORESCENT STAINING
o POST-TRANSPLANT LYMPHOPROLIFERATIVE TO DETECT THE CM V LOWER MATRIX PROTEIN PP65 IN
DISORDERS (PTED) IN PATIENTS WHO HAVE RECEIVED INFECTED LEUKOCYTES (PERIPHERAL BLOOD OR CEREBRAL
HEMATOPOIETIC STEM CELL OR SOLID ORGAN SPINAL FLUID
TRANSPLANTS. ● MOLECULAR METHODS
o DNA OR MRNA
CYTOMEGALOVIRUS o REAL TIME PCR
● UBIQUITOUS VIRUS WITH WORLDWIDE DISTRIBUTION o QUANTITATIVE POR
● TRANSMISSION THROUGH: ● SEROLOGIC METHODS
o 1. CLOSE, PROCONGED CONTACT WT NECTIOUS BODY o SEMI- OR FULLY AUTOMATED (MICROTITER PLATES OR
SECRETIONS MICROPARTICLE SYSTEMS)
o 2. INTIMATE SEXUAL CONTACT o IGG CMV - PAST CMV INFECTION; IFAN INDIVIDUAL IS AT
o 3. BLOOD TRANSFUSIONS RISK FOR FUTURE INFECTION
o 4. SOLID ORGAN TRANSPLANTS AND
o 5, PERINATAL EXPOSURE FROM INFECTED MOTHER TO VARICELLA-ZOSTER VIRUS
INFANT ● CAUSE OF TWO DISTINCT DISEASES VARICELLA
● ISOLATED IN BODY FLUIDS (SALIVA, URINE, STOOL, VAGINAL (CHICKENPOX) AND HERPES ZOSTER (SHINGLES)
AND CERVICAL SECRETIONS, SEMEN, BREAST MILK, AND ● TRANSMITTED BY INHALATION OF INFECTED RESPIRATORY
BLOOD) SECRETIONS OR AEROSOLS FROM SKIN LESIONS;
● MOST IMPORTANT INFECTIOUS AGENT ASSOCIATED WITH TRANSPLACENTAL TRANS: MAY OCCUR.
ORGAN TRANSPLANTATION (FROM REACTIVATION OF CMV IN ● PRIMARY INFECTION WITH VZV: VARICELLA (A BLISTERLIKE
THE RECIPIENT OR TRANSMISSION OF CMV FROM THE DONOR RASH WITH INTENSE ITCHING AND FEVER); OCCUR DURING
ORGAN) CHILDHOOD
● MOST COMMON CAUSE OF CONGENITAL INFECTIONS ● VESICULAR LESIONS FIRST APPEAR ON THE FACE AND
● MAY OCCUR THROUGH THE PLACENTA TRUNK, AND THEN SPREAD TO OTHER AREAS OF THE BODY
● BY PASSAGE OF THE INFANT THROUGH AN INFECTED BIRTH ● USUALLY MILD AND SELF KIMIRING WAS PRODUCE
CANAL COMPLICATIONS (SECONDARY BACTERIAL SKIN INFECTIONS):
● BY POSTNATAL CONTACT WITH BREAST MILK OR OTHER IN PREGNANT WOMEN, PREMATURE LABOR OR CONGENITAL
MATERNAL SECRETIONS MALFORMATIONS COULD RESULT
LABORATORY METHODS IN IMMUNOCOMPROMISED PX: EXTENSIVE SKIN RASH,
● DIRECT DETECTION OF THE VIRUS (VIRAL CULTURE) - NEUROLOGICAL CONDITIONS, PNEUMONIA, HEPATITIS AND
TRADITIONAL NEPHRITIS
● IDENTIFICATION OF CMV ANTIGENS ● REACTIVATION OF VZY (WITH ACTIVE VIRAL REPLICATION)
● MOLECULAR TESTS FOR CMV DNA HERPES ZOSTER/SHINGLES
● COMPLICATIONS POSTHERPETIC NEURALGIA (DEBILITATING ● CHARACTERISTIC ERYTHEMATOUS; MACULOPAPULAR RASH
PAIN THAT PERSISTS FOR WEEKS, MONTHS, OR EVEN YEARS (APPEARS FIRST ON THE FACE, THEN SPREADS TO THE
AFTER RESOLUTION OF THE INFECTION): TRUNK AND EXTREMITIES)
● VACCINE (STRAIN OF LIVE, ATTENUATED VARICELLA VIRUS), ● USUALLY RESOLVES IN 3 TO 5 DAYS:
1995 - MMRV ● DURING PREGNANCY, MAY HAVE CONSEQUENCES SUCH AS
● DEFINITIVE DIAGNOSIS: IDENTFYING SY OR ONLORITS MISCARRIAGE, STILLBIRTH, OR CONGENITAL RUBELLA
PRODUCTS IN SKIN LESIONS, VESICULAR FLUIDS, OR TISSUE. SYNDROME (CRS)
● OLDER METHODS. ● VACCINE (LIVE, ATTENUATED RUBELLA VIRUS)-MMR, MMRV
o CELL CULTURE - OBSERVATION OF ● LABORATORY FINDINGS
o CHARACTERISTIC CPE o CULTURE OF THE VIRUS,
o MICROSCOPY - MULTINUCLEATED GIANT CELLS o DEMONSTRATION OF VIRAL RNA
CALLED TZANCK CELLS IN STAINED SMEAR o DETECTION OF VIRUS-SPECIFIC ANTIBODIES
● DIRECT IMMUNOFLUORESCENCE STAINING OF SCRAPINGS o CULTURES INOCULATED WITH THROAT SWABS,
FROM VESICULAR DESIONS: WITH MONOCLONAL ANTIBODIES NASOPHARYNGEAL SECRETIONS, OR OTHER CLINICAL
DIRECTED AGAINST VIZV ANTIGENS RAPID MORE SENSITIVE SPECIMENS
AND SPECIRIC o REPLACED CULTURE WITH VIRAL NUCLEIC ACID CAN
● REAL-TIME POR FOR ZV DNA (HIGHLY ACCURATE, SENSITIVE, BE ENTIRED BY RT-PCR (MOST WIDELY USED MOLEG;
RAPID) METHOD) OR VIRAL PROTEINS (TEA OR BIA)
● QUANTITATIVE REAL-TIME PCR ● SEROLOGIC TESTS:
● SEROLOGIC TESTING: TOTAL VZV ANTIBODY (CONSISTS o HEMAGGLUTINATION INHIBITION (HI)
PRIMARILY OF IGG) o LATEX AGGLUTINATION
● FLUORESCENT ANTIBODY TO MEMBRANE ANTIGEN (FAMA) - o IMMUNOASSAYS (ELISA-MOST COMMON SEROLOGIC
MOST SENSITIVE AND TEST)
● RELIABLE METHOD OF DETECTING VZV ANTIBODY ● RUBELLA-SPECIFIC IGM ANTIBODIES/FOUR-FOLD INCREASE
● ELISA - MOST COMMONLY USED METHOD TO DETECT VZV IN TITER OR IGG AB
ANTIBODIES o INDICATES PRIMARY RUBELLA INFECTION
● IGG ANTIBODIES- PROVIDE IMMUNITY AND PERSIST FOR LIFE
OTHER VIRAL INFECTIOUS: RUBELLA (ANTIBODY LEVEL OF 10 TO 15 10/ML):
● A SINGLE STRANDED ENVELOPED RNA VIRUS OTHE GENUS
RUBIVIRUS; RUBEOLA VIRUS
● BELONGING TO THE FAMILY TOGAVIRIDAE ● SINGLE STRANDED RNA VIRUS BELONGING TO THE GENUS
● TRANSMISSION RESPIRATORY DROPLETS OR THROUGH MORBILLIVIRUS IN THE PARAMYXOVIRIDAL FAMILY
TRANSPLACENTAL INFECTION ● TRANSMISSION BY: DIRECT CONTACT WITH ABROSOLIZED
● OF THE FETUS DURING PREGNANCY DROPLETS FROM RESPIRATORY SECRETIONS
● CAUSE OF THE TYPICALLY BENIGN, SELF-LIMITED DISEASE ● EPITHELIAL CELLS OF URT (INITIAL) BLOOD - MULTIPLE SITES
THAT IS ALSO KNOWN AS GERMAN (SKIN; LYMPH NODES, AND LIVER)
● MEASLES ● CAUSE OF MEASLES
● DISEASE OF YOUNG CHILDREN ● INCUBATION PERIOD OF 10 TO 12
● INCUBATION PERIOD 12 TO 23 DAYS ● PRODROMAL SYMPTOMS (INCUBATION)
● REPLICATES IN TUE UPPER RESPIRATORY TRACT AND o FEVER, COUGH, CORYZA (RUNNY NOSE), AND
CERVICAL LYMPH NODES, THEN TRAVELS TO THE CONJUNCTIVITIS
BLOODSTREAM
● KOPLIK SPOTS APPEAR ON THE MUCOUS MEMBRANES OF ● CULTURE GOLD STANDARDI CONFIRMATION OF ACUTE
THE INNER CHEEKS OR LIPS INFECTION
● TYPICAL RASH- ERYTHEMATOUS, MACULOPAPULAR ERUPTION ● PREFERRED SPECIMENS BUCCAL SWAB OR SALIVA FROM THE
THAT BEGINS ON THE HAIRLINE, SPREADS TO THE FACE AND BUCCAL CAVITY
NECK, AND GRADUALLY MOVES DOWN THE BODY TO THE ● USED TO INOCULATE CELL LINES SUCH AS PRIMARY MONKEY
TRUNK, ARMS, HANDS, LEGS, AND FEET KIDNEY CELLS AND VERO CHELS
● SUBACUTE SCLEROSING: PANENCEPHALITIS (SSPE) – FATAL ● REPLACED WITH MOLECULAR DETECTION OF VIRAL NUCLEIC
DEGENERATIVE DISORDER OF THE CINS: (PERSISTE ACID
REPLICATION OF MEASLES IN BRAIN) ● STANDARD ANND REAL-TIME PT-PCR METHODS
● MEASLES DURING PREGNANCY- HIGHER RISK OF PREMATURE o PRIMARY DIAGNOSTIC TEST FOR MUMPS
LABOR, SPONTANEOUS ABORTION, OR LOW BIRTH WEIGHT ● SEROLOGIC TESTING (ELISA)
● VACCINE (LIVE, ATTENUATED VIRUS), 1968 - MMR, MMRV o MUMPS SPECIFIC IGM AB/AT LEAST FOURFOLD RISE IN
o 1ST DOSE – 12-15 MONTHS SPECIFIC IGG ANTIBODY CURRENT OR RECENT
o 2ND DOSE - 4-6:YEARS OLD INFECTION (SOLID-PHASE IGMCAPTURE ASSAY
● CELL CULTURE - DIFFICULT AND SLOW o IGG AB - NOT CONFER IMMUNITY, PERSISTS FOR
● SEROLOGICALTESTING YEARS
o RUBBOLA-SPECIRIC IGM ANTIBODIES/FOUR-FOLD RISE
IN IGG ANTIBODY TITER - DIAGNOSIS OF MEASLES HUMAN T-CELL LYMPHOTROPIC VIRUS
o IGM AB - THRU IGM-CAPTURE ELISA METHOD ● HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE THELM LAND
(CURRENT OR RECENT INFECTION) HUMAN T-CEL LYMPHOTROPIC VIRUS TYPE I (HILV-II
o IGG AB - THRU: ELISA (IMMUNITY TO MEASCES BEC: OF RETROVIRUSES:
PAST INFECTION) ● HAVE THREE STRUCTURAL GENES: GAG (VIRAL CORE
● MOLECULAR METHOD: RT-PCR CAN DETECT VIRAL RNA WIN 3 PROTEINS), POL (VIRAL BNZYMES); AND ENV (PROTEINS IN
DAYS OF RASH THE VIRAL ENVELOPE)
● REGION PX (ENCODES SEVERAL REGULATORY PROTEINS
MUMPS VIRUS INCLUDING TAX):
● SIMILAR TO RUBEOLA ● HAS ENZYME, REVERSE TRANSCRIPTASE (RNA-DNA)
● SINGLE-STRANDED RINA VIRUS THAT BELONGS TO THE: ● HTLV-I AND HTLV-II EXIST PREDOMINANTLY IN THE PROVIRAL
PARAMYXOVIRIDAB FAMILY (GENUS RUBULAVIRUS) STATE AND ARE SPREAD DIRECTLY TO UNINFECTED CELLS
● TRANSMITTED THRU: PERSON TO PERSON INPECTED THROUGH A VIRAL SYNAPSE
RESPIRATORY DROPLETS, SALIVA, AND FOMITES AND ● INFECT CDA+ 1 LYMPHOCKTES ALSO CD8 DENDRNIC CHTTS
REPLICATES INITIALLY IN THE NASOPHARYNX AND REGIONAL AND MACRORNGES
LYMPH NODES) ● TRANSMITTED THRU
● INCUBATION PERIOD: 14 TO 18 DAYS o BLOODBORNE (MAINLY THROUGH TRANSFUSIONS
● FROM THE BLOOD TO VARIOUS TISSUES (MENINGES OF THE CONTAINING CELLULAR COMPONENTS/THROUGH
BRAIN, SALIVARY GLANDS, PANCREAS, TESTES, AND OVARIES) INTRAVENOUS DRUG ABUSE)
AND PRODUCES INFLAMMATION AT THOSE SITES: o SEXUAL CONTACT (MOST COMMONLY FROM MEN TO
● PAROTITIS INBLAMMATION OF PARONID GLAND) - MOST WOMEN
COMMON CUNICA MANIPESTATION OF MUMPS o MOTHER-TO-CHILD (MAINLY THROUGH
● IN PREGNANT WOMEN, INCREASED RISK OF FETAL DEATH, BREASTFEEDING)
NOT ASSOCIATED WITH CONGENITAL ABNORMALITIES: ● HTLV-I INPECTION - ENDEMIC IN SOUTHWESTER JAPAN THE
● VACCINE LIVE, ATTENUATED MUMPS VIRUS, 1967 - MMR, MMRV CARIBBEAN ISLANDS, SOUTH AND CENTRAL AFRICA, THE
 MIDDLE BAST, PARTS OR SOUTH AMERICA PAND PAPUA NEW o Group O (The Outlier Group)
GUNNEA o Group N
● HTLV II: VARIOUS NATIVE INDIAN POPULATIONS IN THE o Group P
AMERICAS, A FEW PYGMY TRIBES IN CENTRAL AFRICA, AND o HIV-2 (discovered in 1986) is less pathogenic and has a
INTRAVENOUS DRUG ABUSERS IN NORTH AMERICA AND lower rate of transmission.
EUROPE: ● THREE ROUTES:
● HTLV-I IS THE MAIN CAUSE OF ADULT TO 1. Sexual transmission
CLIBUKEMINTYPHOMA (ATL) AND HTLV: ASSOCIATED 2. Transmission through blood
MYELOPATHY/TROPICAL SPASTIC PARAPARISIS (HAM/TSP). 3. Maternal transmission
● ATL CAN BE CLASSIFIED INTO: ACUTE, LYMPHOMATOUS, o Intimate sexual contact - majority of cases: vaginal/anal
CHRONIC AND SMOLDERING intercourse
● MONOCLONAL PROLIFERATION OF MATURE: T CELLS THAT o Presence of other STDs increases the likelihood of
EXPRESS THE SURFACE MARKERS, CD3, CD4, AND CD25 transmission by disrupting, protective mucous membranes
● HTLV-I IS ALSO ASSOCIATED WITH A VARIETY OF AUTOIMMUNE and activating immunologic cells in the genital areas
AND INFLAMMATORY DISORDERS (UVEITIS - INTRAOCULAR o Contact with blood or other body fluids - occurs mainly
INFLAMMATION OF THE EYES; INFECTIVE DERMATITIS; through sharing of contaminated needles by intravenous drug
MYOSITIS INFLAMMATION OF THE MUSCLES; AND users
ARTHROPATHY-INFLAMMATION OF THE JOINTS) o Increased risk of transmission: 1. Exposures involving a large
● CULTURE - SOPHISTICATED TECHNIQUES (ACANNOT quantity of blood, hollow-bore needles placed directly into an
PERFORMED IN ROUTINE LABS) artery or vein, or deep tissue injury. 2. Source patient is in the
● SEROLOGIC TESTING - EIA AND CLIA (TEST FOR HTEV I AND acute or advanced stages of HIV infection (amount of virus
HTEV-2 ANTIBODIES) circulating in the bloodstream is high)
● PARTICLE AGGLUTINATION TESTS o Perinatally (from infected mother to infant) - 1. Can occur
● CONFIRMATORY TESTS. WESTERN BLOT, LINE during pregnancy 2. By transfer of blood at the time of
IMMUNOASSAYS (LIA) AND IFA delivery 3. Through breastfeeding.
● TESTS CHARACTERISTICS OF HIV
● SAMPLE POSITIVE FOR HTLV-I AB- VISIBLE BANDS ARE COMPOSITION OF THE VIRUS
PRODUCED FOR ONE OF THE ENV PROTEINS EITHER GP46 OR ● Genus Lentivirinae of the virus family Retroviridae (retrovirus)
GP62/68) AND ONE OF THE GAG PROTEINS (EITHER P19, P24, o 1. Contains ribonucleic acid (RNA) as its nucleic acid
OR P 53) o 2. Has a unique enzyme, called reverse transcriptase, which
● TO CLARIFY INDETERMINATE RESULTS: PCR transcribes the viral RNA into DNA.
● Spherical particle (100 to 120 mm in diameter) contains an inner core
LABORATORY DIAGNOSIS OF HIV INFECTION with two copies of single-stranded RNA surrounded by a protein coat
or capsid and an outer envelope of glycoproteins embedded in a lipid
HIV (HUMAN IMMUNODEFICIENCY VIRUS) bilayer.
● Etiologic agent of AIDS (ACQUIRED IMMUNODEFICIENCY VIRUS) STRUCTURAL GENES
• HIV-1 was identified by the laboratories of Luc Montagnier ● HIV GENOME INCLUDES THREE MAIN STRUCTURAL GENES:
(1983) of France and Robert Gallo And Jay Levy (1984) of gag, env, and pol-and a number of regulatory genes
the United States. ● HIV genes and their gene products:
● Four groups of isolates: ● gag gene
o Group M (the main or major group) - responsible for majority o Codes for p55, a precursor protein with a molecular weight of
of HIV-1 infections worldwide 55 kd, from which four core structural proteins are formed: p6,
o Nine subtypes or clades, designated a, b, c, d, f, g, h, j, and k. p9, p17, and p24
 o Codes for nucleocapsid and core proteins ● Homology between HIV-1 and HIV-2 is approximately 50%. (env
● env gene differs greatly)
o Codes for viral envelope proteins
o Codes for glycoproteins gp160, gp120, and gp41 VIRAL REPLICATION
o gp160 is precursor protein that is cleaved to form gp12- and 1. Virus attaches to a susceptible host cell (host cell cd4 antigen and gp
gp41 (attachment and fusion on host cells) 120 glycoproteins on the outer envelope of virus)
o Characteristics of hi vp160 is precursor protein that is cleaved
T helper (Th) cells are the main target for HIV infection (express high
to form
numbers of cd4 molecules on their surface and bind the virus with high
o Gp120 forms the numerous knobs or spikes that protrude affinity)
from the outer envelope
o gp41 is a transmembrane glycoprotein that spans the inner T-tropic or X4 strains - HIV viruses that preferentially infect t cells; m-tropic
and outer membrane and attaches to Gp120. or r5 strains - strains that can infect both macrophages and t cells
● pol gene
• Codes for viral enzymes necessary for viral replication 2. Additional binding step thru co-receptors (chemokine receptors) that
promote fusion of the
• Reverse transcriptase (p51)
HIV envelope with the plasma cell membrane.
• Ribonuclease (RNAse H; p66) - an enzyme involved in the
degradation of the original HIV RNA ● CXCR4 (required for HIV to enter t lymphocytes); ccr5 (required for
• Integrase (p31) - an enzyme which mediates the integration entry into macrophages)
of viral DNA into the genome of infected host cells
• Protease (p10) - cleaves precursor proteins into smaller 3. Viral particle is taken into the cell and uncoating of the particle exposes the
active units used to make the mature virions viral genome.
o
4. Action of the enzyme reverse transcriptase produces complementary DNA
from the viral RNA.

5. Double-stranded DNA is synthesized and, with the help of the HIV

integrase enzyme, becomes integrated into the host cell's genome as a
provirus.

6. Viral DNA within the cell nucleus is then transcribed into genomic RNA and
messenger RNA (mRNA), which are transported to the cytoplasm.
(transcription)

7. Translation of mRNA occurs, with production of viral precursor proteins and

assembly of viral particles.
8. Intact virions bud out from the host cell membrane and acquire their
envelope during the process.

9. Precursor proteins are cleaved by the viral protease enzyme in the mature
virus particles. (viruses can proceed to infect additional host cells)

IMMUNOLOGIC MANIFESTATIONS
IMMUNE RESPONSES TO HIV
● Increased levels of p24 antigen and viral RNA in the host's
CHARACTERISTICS OF HIV bloodstream - initially detected upon viral replication
 ● B Lymphocytes produce antibodies to HIV (detected in the host's
serum by 6 weeks after primary infection). EARLY HIV INFECTION
o 1. Antibodies directed against the gp41 transmembrane ● Forgetfulness poor concentration
glycoprotein ● Apathy psychomotor retardation
o 2. Antibodies to the gag proteins such as p24 ● Withdrawal
o 3. Antibodies to the env, pol, and regulatory proteins LATE DISEASE
● Confusion
● Viral envelope proteins - most immunogenic (can induce production of
● Disorientation
neutralizing antibodies)
● Seizures
● these prevent the virus from infecting neighboring cells.
● Dementia gait disturbances
● T-cell-mediated immunity (CD8+ cytotoxic T lymphocytes or
● Ataxia paraparesis
CYTOLYTIC T CELLS (CTLS)) appear within weeks of HIV infection -
associated with a decline in the amount of HIV in the blood during
SYMPTOMS OF AIDS IN INFANTS INCLUDE:
acute infection ● Failure to thrive, persistent oral candidiasis, hepatosplenomegaly,
● Innate immune defenses - NK and dendritic cells lymphadenopathy, recurrent diarrhea, or recurrent bacterial infections
● EFFECT OF HIV ON THE IMMUNE SYSTEM ● Neurological findings may be present
o Hindered by the rapid mutation
o Downregulating production of Class I MHC molec.
o Cells that can harbor HIV as a silent provirus
● Decrease in CD4 Th cell population is the hallmark feature of HIV
infection.
● Decreased effectiveness of both antibody- and cell-mediated immune
responses.
CLINICAL SYMPTOMS OF HIV INFECTION
ACUTE/EARLY STAGE OF INFECTION
● Rapid burst of viral replication (high levels of circulating virus/viremia
can be seen in the blood)
● HIV begins to disseminate to the lymphoid organs.
● Reduction in cd4 count, then returns to slightly decreased to normal

CLINICAL LATENCY
● Decrease in viremia
● Clinical symptoms are subtle or absent.
● Cd4 cell count remains stable, then progressively declines
● Long-term nonprogressors (LTNP) - have normal/mildly depressed
cd4 t-cell counts and low viral loads; asymptomatic for more than 10
years in the absence of art.
AIDS
● Final stage of infection
● Profound immunosuppression with very low numbers of cd4 t cells
● A resurgence of viremia
● Life-threatening infections and malignancies

HIV-infected individuals often demonstrate neurological symptoms

 2. Use of antiretroviral drugs for preexposure prophylaxis (prep) to
prevent transmission to individuals who are HIV-negative but at a high
risk of contracting the infection
3. PROPHYLACTIC THERAPY WITH ANTIRETROVIRAL DRUGS IS
ALSO OFFERED TO HEALTH-CARE WORKERS WHO MAY. HAVE
BEEN EXPOSED TO HIV THROUGH PERCUTANEOUS OR
MUCOUS MEMBRANE
● Stage 0 - with early HIV infection who had an initial confirmed
VACCINE - ULTIMATE MEANS OF PREVENTING INFECTION
HIV-positive laboratory result followed by a negative or indeterminate
HIV test result within a 6-month period. LABORATORY TESTING FOR HIV INFECTION
o Can be reclassified in one of the other categories (1,2,3) 180 ● SCREENING AND DIAGNOSIS
days or more after initial diagnosis • HIV ANTIBODY TESTING is used in the initial diagnosis of
TREATMENT AND PREVENTION HIV infection.
• ELISA OR RAPID TEST KITS
• Western Blot Test - was the standard confirmatory test for
HIV; replaced.
• Serologic testing for p24 antigen and nucleic acid testing for
HIV RNA have been incorporated into the initial HIV testing.

● TESTING ALGORITHMS
• A combination of laboratory tests performed in sequence to
screen for the presence of HIV infection and resolve any
discrepant results
• 1989, ELISA for HIV-1 antibody, + sample being confirmed by
western blot/HIV-spec.
● Administration of antiretroviral therapy (ART) to suppress viral • Ifa.
replication. • 2004, HIV-1/HIV-2 antibody test, + sample being confirmed by
● More effective regimens involve a combination of drugs from at least western blot/IFA.
two of the antiretroviral drug classes "combination antiretroviral • 2014, combination IA (antibodies to hiv-1 and HIV-2 and
therapy (CART) / highly active antiretroviral therapy (HAART)" HIV-1 p24 antigen) - for adults and children older than 2 yrs
● Goal: to reduce the patient's HIV viral load to a level that is below the old
detectable limit of quantitative plasma viral load assays • If +, sample to undergo rapid/differentiation IA that
EFFECT OF CART discriminates HIV-1 from hiv-2.
● A significant decline in the incidence of opportunistic infections, a • If + on combination IA, (-) on 2nd test, sample is to undergo
delay in progression to aids, and decreased mortality in patients who NAT (nucleic acid testing).
have received treatment.
● Recommended for all HIV-infected persons at the time of diagnosis 1. It allows for earlier detection of infections, as the time between
● Has impact in reducing perinatal transmission exposure and detectable results on the hiv-1/2/p24 combo assay is
APPROACHES IN DEALING WITH HIV typically between 15 and 17 days.
1. Community-based education aimed at high-risk groups 2. It overcomes the limitations associated with use of the western blot
test. (a lengthy procedure that is typically performed only by
specialized reference laboratories)
 3. Western blot testing is less sensitive than the initial ELISA used for ● Can simultaneously detect HIV-1 antibodies, HIV-2 antibodies, and
screening. p24 antigen
SEROLOGICAL TEST PRINCIPLES ● Employ a sandwich ELISA or CLIA
ELISA AND CLIA ● Patient serum is incubated with a solid phase onto which synthetic or
● ELISA - cornerstone of screening procedures for HIV bec: recombinant HIV-1 antigens, HIV-2 antigens, and a monoclonal
o 1. Easy to perform antibody to HIV-1 p24 have been attached.
o 2. Can be adapted to test a large number of samples ● Following a wash step to remove excess sample, a conjugate
o 3. Are highly sensitive and specific containing chemiluminescent- or enzyme-labeled anti-p24 and
HIV-1/HIV-2 antigens is added. After a second incubation and wash
Five generations of ELISA step, the appropriate trigger solution or substrate/stop solution is
added and the relative light units released or optical absorbance is
1ST GENERATION
measured.
● Based on a solid-phase, indirect-assay system that detected
● Used in the initial step of the 2014 laboratory testing algorithm
antibodies to only HIV-1
5TH GENERATION
● HIV antibodies in patient serum were detected after binding to a solid
● bead-based immunoassay that can detect both HIV antibodies and
support coated with viral lysate antigens from HIV-1 cultured in
antigens, in addition can differentiate between HIV-1 and HIV-2
human t-cell lines, followed by addition of an enzyme-labeled
infection.
anti-human igg conjugate and substrate.
Rapid tests for HIV antibodies
● Cons: prone to false-positive results caused by reactions with hla
● Simple, rapid methods (provide results within 30 minutes); detect
antigens or other components from the cells used to culture the virus;
antibodies to HIV-1 alone or to both HIV-1 and HIV-2; can be used on
they were unable to detect antibodies to HIV-2.
serum, plasma, whole blood samples obtained by venipuncture or
2ND GENERATION
fingerstick (for some kits, oral fluid
● Indirect binding assays that used highly purified recombinant or
● Lateral flow or flow-through immunoassays that produce a
synthetic antigens from both HIV-1 and HIV-2, rather than crude cell
colorimetric reaction in the case of a positive result.
lysates
● Interpretation of the results is made through visual observation of the
● Cons: decreased sensitivity (samples containing antibodies to certain
test device and does not require instrumentation
subtypes of
● Highly sensitive and specific
● HIV that lacked the limited antigens used in the assays were tested)
● Cons: false positives and false negatives can occur
3RD GENERATION
● Use the sandwich technique, based on the ability of antibody to bind ● Western blot test (1984)
with more than one antigen. o Most common method used for systematic confirmation of
● Available in ELISA and CLIA formats positive ELISA results from 1985 to 2014
● Antibodies in patient serum or plasma bind to recombinant HIV-1 and o 1. Nitrocellulose or nylon strips containing individual HIV
HIV-2 proteins coated onto a solid phase. After washing, enzyme or proteins blotted onto the test membrane
chemiluminescent-labeled HIV-1 and HIV-2 antigens are added and o 2. Any HIV antibodies present in the sample will bind to their
bind to the already bound HIV-specific patient antibodies. Substrate corresponding antigens on the test membrane.
(or trigger solution, if CLIA is used) is added, and the color o 3. Washing procedure. (unbound ab is removed)
development (or release of light with CLIA) is proportional to the o 4. Anti-human immunoglobulin with an enzyme label is added
amount of antibody in the sample directly to the test strip and binds to specific HIV antibodies
● Improves sensitivity by simultaneously detecting HIV antibodies of from the patient sample.
different immunoglobulin classes, including IgM o 5. Washing procedure. (unbound conjugate is removed)
4TH GENERATION o 6. Bound conjugate is detected after adding the appropriate
substrate. (producing chromogenic reaction)
● Antibodies to the gag proteins p24 and p55
 o Appear early after exposure to the virus, but decrease or ● If serological results are inconclusive such as in very early infection or
become undetectable as clinical symptoms of aids appear. in the diagnosis of infants, where presence of maternal antibodies can
● Antibodies to the envelope proteins gp41, gp120, and gp160 confuse test results
o Appear slightly later but remain throughout all disease stages ● Used to resolve discrepancies between a positive result in the initial
in an HIV-infected individual antigen-antibody combo assay and the follow-up HIV-1/HIV-2
● A more reliable indicator of the presence of HIV antibody differentiation assay
● HIV-1 antibody/HIV-2 antibody/p24 antigen test is nonreactive, but the
Visual interpretation and densitometry NAT is reactive, then this result is considered evidence for acute
● Visual interpretation and densitometry can be performed to identify HIV-1 infection.
the number and types of antibody produced. ● HIV-1/HIV-2 antibody test is indeterminate and the NAT is reactive,
● Performed only in specialized reference laboratories. this suggests that HIV-1 antibodies were indeed present
● Positive and negative control sera must be included in the test run ● HIV-1/HIV-2 antibody test is reactive or indeterminate and the NAT is
(quality control) nonreactive, the initial test is a false-positive one.
o Valid if: ● Qualitative Polymerase Chain Reaction (PCR)-based assay to screen
▪ The negative control should produce no bands donors of whole blood, blood
▪ The positive control should be reactive with p17, p24,
p31, gp41, p51, p55, p66, and gp120/160
● Negative test result for the patient sample is reported if either no
bands are present or if none of the bands present correspond to the
molecular weights of any of the known viral proteins.
● Specimens that have some of the characteristic bands present but do
not meet the criteria for a positive test result are considered to be
indeterminate. (false positive caused by cross-reacting antibodies)
● Antibodies to the gag proteins p24 and p55
o Appear early after exposure to the virus, but decrease or
become undetectable as clinical symptoms of aids appear.
● Antibodies to the envelope proteins gp41, gp120, and gp160
o Appear slightly later but remain throughout all disease stages
in an HIV-infected individual

CONS OF WESTERN BLOT:

● Relative insensitivity
● level of technical difficulty
● long turnaround time to obtain results

CDC has recommended that the western blot be replaced with rapid
HIV-1/HIV-2 antibody tests as the standard method for confirmation of positive
screening results.

QUALITATIVE NUCLEIC ACID TESTS (NAT)

● Used to determine whether or not a detectable level of HIV nucleic
acid is present in human plasma.
● Used to screen for infection or make an initial patient diagnosis