TRI UMIANA SOLEHA

DEPT. OF MICROBIOLOGY
MEDICAL FACULTY LAMPUNG
UNIVERSITY
 KEY CONCEPTS
• PREFERENTIALLY BINDS TO THE CD4 RECEPTOR
FOUND ON HELPER T CELLS & MONOCYTES; THE
DESTRUCTION OF THESE CELLS ULTIMATELY
DISABLES THE IMMUNE SYSTEM & MAKES THE
INFECTED INDIVIDUAL VULNERABLE TO
OPPORTUNISTIC INFECTIONS
• TRANSMITTED THROUGH SEXUAL CONTACT, IV DRUG
USE, VERTICALLY (MOTHER TO CHILD)
• DISPLAY ANTIGENIC VARIATION
• HAS A LONG LATENCY PERIOD (AVERAGE 10 YEARS)
• CAN CURRENTLY BE MANAGED WITH ANTIVIRAL
DRUGS BUT IS OTHERWISE NEARLY 100% FATAL
 INTRODUCTION
HIV NONONCOGENIC RETROVIRUS
RETROVIRIDAE - LENTIVIRINAE
ROBERT GALLO ET AL (1978) : ISOLATED
RETROVIRUS FROM THE LYMPHOCYTES OF
LEUKEMIA PATIENT HTLV-I
A SECOND VIRUS : HTLV-II WAS ISOLATED IN
SEATTLE USA FROM THE CELLS OF PATIENT
WITH A RARE “HAIRY CELL” LEUKEMIA
THE ILLNESS OF AIDS WAS FIRST DESCRIBED IN
MALE HOMOSEXUALS IN 1981, AND THE
VIRUS WAS ISOLATED BY THE END OF 1983
ESSEX ET AL (1983) : 25 – 30 % AIDS AG-AB
MEMBRANE HTLV-I
 INTRODUCTION
THE FIRST ISOLATION OF RETROVIRUS FROM AIDS
CASE WAS MADE BY LUC MONTAGNIER & BARRÉ-
SINOUSSI AT THE PASTEUR INSTITUTE PARIS
(1983) LAV
THE VIRUS ISOLATED FROM HAEMOFILIA
PATIENT WITH LYMPHADENOPATHY
IT WAS QUICKLY CONFIRMED BY ROBERT GALLO
(1984) HTLV-III
LEVY (1984) : ISOLATED AIDS-RELATED
RETROVIRUS ARV
LUC MONTAGNIER (1986) ISOLATED A FOURTH
HUMAN RETROVIRUS FROM AIDS IN WEST
AFRICA
HIV-2
 CLASSIFICATION

Subfamily Disease caused Natural hosts

Oncovirinae
HTLV-I Adult T-cell leukemia, Human
lymphoma, tropical
spastic paraparesis
HTLV-II Hairy cell leukemia Human
Inapparent
Spumavirinae Primates & other
persistent infection animals
Lentivirinae
HIV-1 Immunodeficiency Human
HIV-2 Immunodeficiency Human & primates
Monkey
SIV Immunodeficiency
THE HUMAN AIDS VIRUS ARE NOT HOMOGENOUS, MOST ARE VARIANTS OF HIV-1
A SECOND VIRUS HIV-2 SEEMS PREVALENT ONLY IN WEST AFRICA, MUCH LESS
VIRULENT
ONLY ABOUT 40% OF THE SEQUENCES OF HIV-1 AND HIV-2 ARE IDENTICAL
BASED ON ENV GENE SEQUENCES
9 SUBTYPES OF HIV-1 A–I
5 SUBTYPES OF HIV-2 A–E
THESE SUBTYPES ARE REFERRED AS “CLADES”. WITHIN SUBTYPE THERE IS EXTENSIVE
VARIABILITY
 PROPERTIES OF HIV
VIRION : SPHERICAL, 80 – 100 NM, CYLINDRIC CORE
GENOME : SS-RNA, LINEAR, POSITIVE SENSE, 9 – 10 KB
PROTEINS : ENVELOPE GLYCOPROTEIN, REVERSE
TRANSCRIPTASE ENZYME CONTAINED INSIDE VIRIONS,
PROTEASE REQUIRED FOR PRODUCTION OF INFECTIOUS
VIRUS
ENVELOPE : PRESENT
REPLICATION : REVERSE TRANSCRIPTASE MAKES DNA
COPY FROM FROM GENOMIC RNA; PROVIRUS DNA IS
TEMPLATE FOR VIRAL RNA
MATURATION : PARTICLES BUD FROM PLASMA MEMBRANE
STRUCTURE OF HIV
THE VIRUS CONTAINS THE THREE GENES REQUIRED FOR A
REPLICATION
 GAG : ENCODES THE CORE PROTEIN
(GROUP-SPECIFIC ANTIGENS
 POL : ENCODES THE REVERSE
TRANSCRIPTASE ENZYME (POLYMEASE)
 ENV : ENCODES THE GLYCOPROTEINS THAT
FORM PROJECTIONS ON THE ENVELOPE OF
THE PARTICLE
UP TO SIX ADDITIONAL GENES REGULATE VIRAL EXPRESSION &
IMPORTANT IN DISEASE PATHOGENESIS IN VIVO. ALTHOUGH
THESE AUXILIARY GENES SHOW A LITTLE SEQUENCE HOMOLOGY
AMONG LENTIVIRUS, THEIR FUNCTIONS ARE CONSERVED
 ADDITIONAL GENES :
 TAT OR TAX : TRANSACTIVATING REGULATORY GENE ENCODES A
NONSTRUCTURAL PROTEINS THAT ALTERS THE TRANSCRIPTION
OR TRANSLATIONAL EFFICIENCY OF OTHER VIRAL GENE
 REV : REGULATOR OF EXPRESSION OF VIRION

 GP 120 : RESPONSIBLE FOR VIRUS ATTACHMENT TO

THE CD4 MOLECULE AND CORECEPTORS & CARRIES
THE MAJOR ANTIGENIC DETERMINANTS THAT ELICIT
NEUTRALIZING ABS
 GP 41 : CONTAIN TRANSMEMBRANE DOMAIN THAT
ANCHORS THE GLYCOPROTEIN IN THE VIRAL ENVELOPE AND A
FUSION DOMAIN THAT FACILITATE VIRAL
PENETRATION INTO TARGET CELLS
VIRAL REPLICATION
 DISINFECTION & INACTIVATION
 HIV COMPLETELY INACTIVATED BY TREATMENT FOR 10 MINUTES AT ROOM TEMPERATURE
WITH :
 10 % HOUSEHOLD BLEACH
 50 % ETHANOL
 35 % ISOPROPANOL
 0,5 % LYSOL
 0,5 % PARAFORMALDEHYDE
 0,3 % HYDROGEN PEROXIDE

ALSO INACTIVATED BY EXTREMES PH : PH 1.0 & 13.0

WHEN HIV PRESENT IN CLOTTED OR UNCLOTTED BLOOD IN
NEEDLE OR SYRINGE, EXPOSURE TO UNDILUTED BLEACH AT LEAST
30 SECONDS FOR INACTIVATION
HIV INACTIVATED BY HEATING AT 560C FOR 10 MINUTES
 CELL TROPISM
• IN VITRO
 T LYMPHOCYTE, CD4+
 MONOCYTE/MACROPHAGE
 MICROGLIA
 PRECURSOR CD 34+ CELLS
 MONOCYTIC & T-CELL LINES
 GLIOMA & NEUROBLASTOMA CELL
LINES
 TUMOR CELL LINES
• IN VIVO
 T LYMPHOCYTE, CD4+
 MONOCYTE/ MACROPHAGE
 EPITHELIAL LANGERHANS CELLS
 DENDRITIC CELLS
 ENDOTHELIAL CELLS OF THE BRAIN
 MICROGLIA, ASTROGLIA,
OLIGODENDROGLIA
 CELLS OF RETINA, CERVIX AND COLON
 IMMUNODEFICIENCY PROCESS
MODE OF TRANSMISSION

 PARENTERAL (IV, DRUG USE)

 MUCOSAL (SEXUAL CONTACT)
 VERTICAL (MOTHER TO CHILD)

FREE HIV HIV IN CD4+ T CELLS

REGIONAL LYMPH NODES

CELLULAR IR HUMORAL IR
 LIMPHOPENIA
 CD4+ CELLS
 FREE VIRUS & P24 IN BLOOD
 NUMBER OF INFECTED CD4

 VIRUS RAPID REPLICATION

WITH CONTROL OF IR

2 – 4 WEEKS

TOTAL LYMPHOCYTE CD8

ANTIBODY + : 2 – 3 WEEKS MONTHS
 PATHOGENESIS & PATHOLOGY
STAGES :
PRIMARY INFECTION
DISSEMINATION OF VIRUS TO LYMPHOID
ORGANS
CLINICAL LATENCY
ELEVATED HIV EXPRESSION
CLINICAL DISEASE
DEATH
THE DURATION BETWEEN PRIMARY INFECTION
& PROGRESSION TO CLINICAL DISEASE ± 10
YEARS
DEATH USUALLY 3 YEARS AFTER ONSET OF
CLINICAL SYNDROME
• FOLLOWING PRIMARY
INFECTION, VIRAL REPLICATION
OCCURS & VIREMIA DETECTABLE
FOR ABOUT 8 – 12 WEEKS
• VIRUS IS WIDELY DISSEMINATED
THROUGHOUT THE BODY & THE
LYMPHOID ORGANS BECOME
SEEDED
• THE PERIOD OF CLINICAL LATENCY MAY
LAST FOR AS LONG AS 10 YEARS. DURING
THIS PERIOD, THERE IS A HIGH LEVEL OF
ONGOING VIRAL REPLICATION, ESTIMATED
THAT 10 BILLION HIV PARTICLES ARE
PRODUCED & DESTROYED EACH DAY.

• THE HALF LIFE OF VIRUS IN PLASMA IS

ABOUT 6 HOURS, AND THE VIRUS LIFE
CYCLE (FROM THE TIME OF INFECTION OF
CELLS TO THE PRODUCTION OF NEW
PROGENY THAT INFECT THE NEXT CELL)
AVERAGES 2.6 DAYS
 CLINICAL FINDINGS
AIDS IS CHARACTERIZED BY A PRONOUNCED
SUPPRESSION OF THE IMMUNE SYSTEM & THE
DEVELOPMENT OF UNUSUAL NEOPLASMS
(ESPECIALLY KAPOSI’S SARCOMA) OR A WIDE
VARIETY OF SEVERE OPPORTUNISTIC
INFECTIONS
• PLASMA VIRAL LOAD :
THE AMOUNT OF HIV IN THE BLOOD (VIRAL
LOAD) IS OF SIGNIFICANT PROGNOSTIC VALUE.
PLASMA HIV RNA LEVELS CAN BE DETERMINED
USING A VARIETY OF COMMERCIALLY
AVAILABLE ASSAYS.
 CLINICAL CATEGORIES OF HIV INFECTION IN
PERSONS > 13 YEARS OF AGE
1. CATEGORY A :
ASYMPTOMATIC
PERSISTENT GENERALIZED ADENOPATHY
SYMPTOMATIC, ACUTE (PRIMARY) HIV INFECTION

2. CATEGORY B :
SOME CONDITIONS ARE DIAGNOSED

3. CATEGORY C :

ANY OF SOME CONDITIONS ARE

DIAGNOSED
 CDC DEFINITION OF AIDS
Clinical category
CD4+ T-cells AB C

500/l A1B1 C1

200 – 499/l A2B2 C2

<200/l A3B3 C3

AIDS IS DIAGNOSED IF THE PATIENT MEETS

CRITERIA FOR CATEGORY A3, B3, C1, C2, OR C3
 OPPORTUNISTIC INFECTIONS
• PROTOZOA • BACTERIA
MYCOBACTERIUM AVIUM-
TOXOPLASMA GONDII INTRACELLULARE
ISOSPORA BELLI MYCOBACTERIUM
TUBERCULOSIS
CRYPTOSPORIDIUM SP. LISTERIA MONOCYTOGENES
NOCARDIA ASTEROIDES
SALMONELLA SP.
• FUNGI
STREPTOCOCCUS SP.
CANDIDA ALBICANS
CRYPTOCOCCUS • VIRUS
NEOFORMANS CYTOMEGALOVIRUS
COCCIDIOIDES IMMITIS HERPES SIMPLEX VIRUS
HISTOPLASMA VARICELLA-ZOSTER VIRUS
CAPSULATUM ADENOVIRUS

PNEUMOCYSTIS CARINII JC HUMAN PAPOVAVIRUS

HEPATITIS B VIRUS
 LABORATORY DIAGNOSIS

EVIDENCE OF HIV INFECTION :

1. VIRUS ISOLATION
CULTURED FROM LYMPHOCYTE IN PERIPHERAL BLOOD
OR OTHER SPECIMENS, BUT TIME CONSUMING

2. SEROLOGIC DETERMINATION OF ANTIVIRAL

ABS
ELISA, ANTIBODY REPEATED
CONFIRMATION : IMMUNOFLUORESCENCE &
RADIOIMMUNOPRECIPITATION,
WESTERN BLOT : AT LEAST 2 BANDS OF P24, GP41 OR
GP120/GP 160 SHOULD BE PRESENT

3. MEASUREMENT OF VIRAL NUCLEIC ACID OR AG

RT-PCR
 LABORATORY DIAGNOSIS

EXAMINATION OF IMMUNITY STATUS

- CD4, CD8
- HEMATOLOGY

EXAMINATION OF OPPORTUNISTIC INFECTION /

MALIGNANCY
 INTERPRETATION OF LABORATORY EXAMINATION
1. POSITIVE HIV INFECTION :
 PATIENT SERA UP TO 15 MONTHS OF AGE, HIV +, EVEN
MOTHER HAS NO HIV
 PATIENT SERA < 15 MONTHS OF AGE, HIV +, MOTHER
HIV +, LYMPHOCYTE COUNT 
 P24 AG +
 HIV CULTURE +, AG +, RT-ASE ENZYME +, PROBE +
 POSITIVE TEST WITH SPECIFIC TESTS
2. NEGATIVE HIV :
SCREENING & CONFIRMATION TESTS -
3. INCONCLUSIVE :
 SCREENING TEST FOR HIV +, CONFIRMATION, AG, &
CULTURE ARE NEGATIVE
 BABY < 15 MONTH OF AGE HIV -, MOTHER HIV +
 ANTIRETROVIRUS DRUG FOR HIV
INFECTION
NNRTI (NON-NUCLEOSIDE ANALOG REVERSE TRANSCRIPTASE
INHIBITOR)
* NEVIRAPINE
* DELAVIRDINE MESYLATE
NRTI (NUCLEOSIDE ANALOG REVERSE TRANSCRIPATSE
INHIBITOR)
* DIDANOSINE (DDI)* LAMIVUDINE (3TC)
* ZALZITABINE (DDC) * STAVUDINE (D4T)
* ZIDOVUDINE (AZT : AZYDOTHYMIDINE
PROTEASE INHIBITOR
* INDINAVIR * RITONAVIR
* NELFINAVIR MESYLATE * SAQUINAVIR