MT-MICRO 2 (Finals) - Naked DNA

 Parvoviridae
Introduction to Virology  Papovaviridae
 Adenoviridae
Virus - Enveloped DNA
 Submicroscopic  HSV
 Obligate intracellular  Hepadnaviridae
 Smallest of all infectious agents  Poxviridae
 Viral structure  RNA viruses
- 0.01-0.03 micrometer - Genome structure determines the mechanism,
 Filterable agent transcription, and replication
- Virion – viral particle - Labile and transient
 Inner nucleic acid - Release in the cytoplasm (mostly)
core – RNA or DNA - Can’t replicate RNA
 Capsid – protect the - Prone to mutation
nucleic acid - Clinically significant RNA virus
o Helical – rod-  Bunyaviridae
shaped  Arenaviridae
o Icosahedral –  Togaviridae
cube-like  Orthomyxoviridae
o Complex – non-conforming symmetry  Flaviviridae
 Envelope – outer membrane  Filoviridae
- Outer membrane  Paramyxoviridae – largest RNA virus
Envelope Naked  Picornaviridae – smallest RNA virus
Ether sensitive/labile Ether resistant  Reoviridae
Unstable Stable  Retroviridae
Direct contact Fecal oral  Rhabdoviridae
 Caliciviridae
Classification  Coronaviridae
 Virus taxonomy - All are single stranded except Reoviridae (dsRNA)
- International Committee on Taxonomy or Viruses - All replicate in the cytoplasm except Retroviridae
(ICTV) and Orthomyxoviridae
- 6 orders (-virales) - Icosahedral
- 87 families (-viridae)  Picornaviridae
- 19 subfamilies (-virinae)  Caliciviridae
- 348 genera (-virus)  Reoviridae
 Retroviridae
 Nucleic acid composition – DNA (double-stranded)
 Togaviridae
or RNA (single-stranded)
 Capsid – helical or isocahedral
Viral Replication
 Envelope
 Attachment
- Presence or absence
 Penetration
- Acquired from nuclear or cytoplasmic membrane
 Uncoating
 DNA virus
- Resembles host DNA for transcription and  Macromolecular
replication synthesis
- Not transient nor labile  Viral assembly
- Viral genomes remain in the infected cells  Release
- Established persistent infection
- DNA genomes reside in the nucleus
- Clinically significant DNA virus
 Herpesviridae
 Hepadnaviridae
 Adenoviridae
 Parvoviridae – smallest DNA virus
 Papillomaviridae
 Poxviridae – largest DNA virus
- All replicate in the nucleus except Poxviridae
(cytoplasm)
- All are double stranded except Parvoviridae

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  Direct detection
- Most rapid method of diagnosis
- Electron microscopy – negative staining
technique (most common method for rapid EM)
- Immunofluorescence – sample are stained with
fluorescence-labeled antibodies
Cytopathic effect Virus
Cowdry type A HSV and VZV
Owl’s eye CMV
Negri bodies Rabies
Koilocytosis HPV

 Nucleic acid base detection

Specimen Collection, Transport, and Storage Advantages Disadvantages
 Specimen STAT Detection of active and
- Throat swabs or washing inactivated virus
 Throat – enteroviruses, adenoviruses, HSV Better sensitivity than cell High cost
 Nasopharyngeal – RSV, influenza, and culture
parainfluenza Detect multiple viruses Complex
 Bronchial and Bronchoalveolar washes – simultaneously
for viruses that infect the lower respiratory Characterize the virus Lacks clearance
tract (influenza and adenovirus) genetically
- Rectal swabs – rotavirus, enteric adenovirus and  Viral isolation
enteroviruses - Gold standard
- Skin scrapings or lesion swabs – CMV, mumps, - Cell culture, animal inoculation, embryonated eggs
rubella, measles, polyomavirus and adenovirus
 Cell culture – grown as monolayer
- Urine – CMV, mumps, rubella, measles,
polyomavirus and adenovirus
- Body fluid or vesicle – enteroviruses, HSV, VZV,
influenza or CMV
- Blood
 CMV, HSV, and VZV
 5-10 mL in heparinized, citrated, or EDTA for
CMV detection
 Citrated for other viruses
- Bone marrow
 Added to tube with heparin, citrate or EDTA
 Primary cell culture
 Most viruses other than parvovirus B19 are
- Same karyotype and chromosome number as the
detected more readily from sites other than
original tissue
bone marrow
- Human embryonic kidney
- Tissue biopsies
- Rabbit embryonic kidney
 Viruses which infect the lungs (CMV, influenza
- Primary monkey kidney
virus, sin nombre virus, the brain (HSV), and
- Rhesus monkey kidney
GIT (CMV)
- Cynomolgus monkey kidney
 Storage – 4°C
- African green monkey kidney
 Transport – -70°C
 Diploid cell lines
Method of Detection
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 - Passage of 1° culture - Provide limited information
- >75% of cells have the same karyotype as the - Use in nonculturable agent
normal cells - Determining immune status
- Human embryonic lung
- Human diploid fibroblast Double Stranded DNA Viruses
 Continuous cell lines
- >75% of cells have the same karyotype as normal Adenoviridae
cells  dsDNA
- Human cervical carcinoma – HeLa  Naked
- Human Laryngeal carcinoma – HEP 2  Icosahedral
- Human nasopharyngeal carcinoma – KB  Posses a long fiber
- Human lung carcinoma – A549  Contain many serotypes (up to 50)
 Cell cultures commonly used in the clinical - Common serotypes include 1-8, 11, 35, 21, 37, 40
virology laboratory - Manifestations depend on age and immune status
Virus PMK HDF  Gastroenteritis in young children in warmer months
Herpes simplex
- +++  First isolated from adenoid tissue
virus  Mode of transmission
Cytomegalovirus - +++ - Fecal-oral
Varicella-zoster - Aerosols
- +++
virus - Close contact
Enterovirus + +  Diseases
Adenovirus + ++ - Acute respiratory disease (serotype 14)
Respiratory  Rare for adenovirus because of cell type 14
± ±
syncytial virus - Epidemic keratoconjunctivitis
Influenza, - Pharyngoconjunctival fever
+++ ±
parainfluenza - Epidemic gastroenteritis (serotype 40 and 41)
 Classified as enteric adenovirus
Virus HEp2 RK  Identification
Herpes simplex - IFA
+++ +++ - EIA
virus
Cytomegalovirus - - - Nucleic acid test
Varicella-zoster  Serotyping
- - - Serum neutralization
virus
Enterovirus ++ - - Hemagglutination inhibition
Adenovirus +++ -  CPE appears swollen in grapelike clusters
Respiratory  Electron microscopy is mostly for research purposes
+++ -
syncytial virus
Influenza, Herpesviridae (HSV)
- -  dsDNA
parainfluenza
 Enveloped
Virus A549 CPE  Icosahedral
Herpes simplex Large, rounded  Latency and lifelong presence
+++ - Can reactivate after primary infection
virus cells
Large, rounded  At least 8 known herpesvirus
Cytomegalovirus - - Common are HSV 1 and 2, primary and recurrent
cells
Foci or rounded infection
Varicella-zoster - Infections above the waist are usually from HSV 1,
± cells; possible
virus below the waist are usually from HSV 2
syncytia
Refractile, round  Mode of transmission
Enterovirus + - Contact to ulceration of mucus membrane and/or
cells in clusters
Large, rounded genitalia
Adenovirus ++  Diseases
cells in clusters
Respiratory - Oral herpes – occurs in mouth, tongue, gums
++ Syncytia - Genital herpes
syncytial virus
Variable—none - Neonatal herpes – C-section is done to reduce
Influenza, infection
- to granular
parainfluenza - Herpetic whitlow (fingers)
appearance
- Herpes encephalitis
- Ocular herpes – can cause blindness
 Serology  Specimen

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 - Aspirates (vesicles and lesions) PB - + ± -
- Conjunctival scraping Anti-VCA IgM - + ± -
 Cell lines Anti-VCA IgG - + + +
- RK Anti-EA-IgG - ± ± -
- HEL Anti-EBNA - - + +
- HEp-2 Interpretation No
- A549 previous Acute
exposure infectious Recent Past
 Varicella-zoster to mononuc- infection infection
- Mode of transmission Epstein- leosis
 Droplet inhalation Barr virus
 Direct contact with lesion - Atypical lymphocytes
- Disease - Paul-Bunell (serological test)
 Chicken pox  Cytomegalovirus (CMV)
 Shingles - Salivary gland virus
- Specimen - Mode of transmission
 Lesions (vesicles)  Close contact with secretion and excretions
- Culture o Saliva
 A-549 o Breast milk
- Tzanc’s smear o Semen
 Epstain-Barr Virus o Stool
- Mode of transmission  Blood transfusion
 Oral contact with saliva  Organ transplants
- Disease - Disease
 Infectious mononucleosis  Disseminated disease
 Burkitt’s lymphoma  Congenital CMV infection
 Hodgkin disease  Infection in HIV and transplant patient
 Nasopharyngeal carcinoma  Self-limiting or patient recovers without
 B-cell lymphoma medical intervention, as long as
- Serological markers immunocompetent (asymptomatic)
 Anti-VCA – antibodies against viral capsid  Causes infectious mononucleosis
antigen  40 days fever –
o IgM – early infection (disappears after 4 mostly seen in
weeks) transplant patient
o IgG – acute stage, can overlap with IgM, - Sample
persist lifelong in low titer  Blood
 Anti-EA IgG – IgG antibody to early antigen  Body fluids
o Seen during acute phase  Urine
o Has current or recent infection  Tissues
o Lasts for 6 months  Respiratory
 Anti-EA/D – antibody to early antigen, diffuse secretions
o Seen in acute phase - Culture
o Current or recent infection  HDF (owl’s eye)
o Lasts for 6 months  Human Herpesvirus 6 and 7
o Elevated levels seen in NPC (elevated IgG - Mode of transmission
and IgA)  Close contact with saliva
 Anti-EA/R – antibody to early antigen, - Disease
restricted  Roseola infantum
o Seen in acute phase  Exanthema subitum
o Disappears after EA/D  Sixth disease
o Can persist up to 2 years or lifelong There are 6 causes of skin rashes
o Elevated in Burkitt lymphoma o 1st – rubeola, measles
 Anti-EBNA – antibody to EBV nuclear antigen o 2nd – scarlet fever, scarletina
o Appear after 1 month o 3rd – rubella, german measles
o EBV and Hepatitis o 4th – SSS
o 5th – exanthema infectiosum
o 6th – roseola
 Mostly in infant in children (3 years old)
 Interstitial pneumonytis in organ transplant
 Leucopenia
- Interpretation of Epstein-Barr virus serologic - Culture of T cell
markers - PCR
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 Human Herpesvirus 8
- Mode of Double Stranded RNA Virus
Transmission
 Sexual contact Reoviridae
- Disease  dsRNA virus
 Kaposi  Segmented (11)
sarcoma  Icosahedral capsid
- Nonculturable but  Naked
can be tested through PCR  No disease could be associated (orphan)
- B-cell
Rotavirus
Poxviridae  The most common cause of viral gastroenteritis in
 dsDNA infants and children (6 months to 2 years old) and
 Enveloped diarrhea during winter months
 Complex  Spread via the fecal-oral route
 Brick-shaped  Replicate in the epithelial cells in the tips of microvilli
 Largest DNA virus of the small intestine
 Variolla
- Mode of transmission Hepatitis
 Direct inhalation or contact with lesions  Hepatitis A virus (HAV)
- Disease - Picornaviridae
 Small pox - Hepatovirus (enterovirus type 72)
- Extinct in nature - Acute viral hepatitis
- Vaccinia (vaccine strain) - Infectious hepatitis
- Short incubation
Papillomaviridae - Low mortality
 dsDNA - Antibody and antigen markers
 Naked  First and most clinically useful is IgM
 Icosahedral antibody to HAV
 Human papilloma virus  IgM indicates acute infection, appears 4-5
- Mode of transmission weeks after exposure
 Close contact  IgM disappears in 3-6 months, replaced by IgG
- Disease anti-HAV
 Laryngeal wart  IgG peaks during convalescence and may
 Veneral wart remain detectable for life
 Cervical carcinoma  Hepatitis B virus (HBV)
- Serotype 16 and 18 - Hepadnaviridae
- Nonculturable - Partly dsDNA
- Pap smears (koilocytes) - Icosahedral capsid
- Naked
Single Stranded DNA Viruses - Virion – dane particle
- Surface antigen – Australia antigen
Parvoviridae - Old tern “serum hepatitis,” incubation period of
 ssDNA virus 4-26 weeks
 Icosahedral capsid - Route of infection is 140,000-320,000 cases per
 Naked year resulting in 5-6,000 deaths a year
 Smallest DNA virus - Duration of acute infection ranges from 4-8 weeks
 Parvovirus B-19 with symptoms similar to HAV
- Principal pathogen - 10% progress to chronic
- Only human parvovirus - One-third of chronic at risk of developing chronic
- Aplastic crises active cirrhosis and/or hepatocellular carcinoma
- Erythema infectiosum (fifth disease) - Involve the detection of three marker system
 Slapped cheek appearance - Hepatitis B surface antigen (HBsAg) is the first
- Named after the serum sample (number 19 of to appear, appears 2-4 weeks during late
panel B) incubation, marker of choice for recent infection
 Initially observe under electron microscope - Anti-hepatitis B surface antigen (anti-HBs) is
- The host cell is RBC precursor and the receptor is the last antibody to appear, may persist for life
the blood group P antigen - Between disappearance of HBsAg and appearance
- Characterized by the decrease in the RBC of anti-HBs is known as the core window
production of the BM

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 - IgM antibody to Hepatitis B core antigen (anti- - Presence of IgM anti-D and HBsAg together with
HBc) may be the only detectable marker during IgM anti-HBc indicates co-infection
the core window, differentiates recent infection - Absence of IgM anti-HBc indicates superinfection
from chronic carrier state - Presence of anti-HD indicates chronic infection
- Third marker is Hepatitis B e-antigen (HBeAg),  Hepatitis C virus (HCV)
appearance of HBeAg and anti-HBe, closely - Non A, Non B hepatitis
coincide with HBsAg - Flaviviridae
Test Acute Hepatitis Past exposure - Clinically and epidemiologically similar to HBV
B (Immunity) - 60-70% of HCV will develop chronic hepatitis, 10-
HBsAg + - 20% cirrhosis, and 15% hepatocellular carcinoma
Anti-HBs - + - HCV and HBV may be present as co-infections
HBeAg + - - Serological profile not fully developed
Anti-HBe - +/- - Presence of HCV antibodies only indicates present
Anti-HBc + + or past infection
IgM anti-HBc + - - Can have false negative in some patients
HBV DNA + -  Hepatitis E virus (HEV)
ALT Elevated Normal - Caliciviridae
- Similar to HAV in transmission and clinical course
Test Previous Chronic - Found primarily in developing countries, Africa
immunization Hepatitis B and Asia
(CHB) - Results in acute hepatitis, no rish of chronic
HBsAg - + hepatitis
- Pregnant women with HEV may develop
Anti-HBs + -
fulminant fever failure and death
HBeAg - +/-
- No distinctive markers, diagnosis based on
Anti-HBe - +/-
symptoms for exposed individuals in endemic
Anti-HBc - + countries
IgM anti-HBc - -
HBV DNA - +/- Single Stranded RNA Viruses
ALT Normal Elevated
Orthomyxoviridae
Test Chronic precore Healthy carrier  Segmented
HBsAg + +  Helical capsid with envelope
Anti-HBs - -  Replicate in nucleus
HBeAg - -  Influenza virus types A, B, and C
Anti-HBe + +  Influenza A virus remains one of the most crucial
Anti-HBc + + health problems worldwide
IgM anti-HBc - -  The influenza virus infects the upper respiratory tract
HBV DNA + - and major central airways in humans, horses, birds,
ALT Elevated Normal pigs, and even seals
 In 1918-1919, an influenza pandemic killed more than
Test Acute delta Chronic delta 120 million people in Alaska and the Pacific Islands
HBsAg + +  Surface antigens
Anti-HBs - - - Hemagglutinin (H) – used to bind host cells
HBeAg +/- -  16 H antigens (H1-H16)
Anti-HBe - +  Human infections usually only occur with H1,
Anti-HBc + + H2, H3
IgM anti-HBc +/- - - Neuraminidase (N) – cleaves budding viruses
HBV DNA +/- Low or - from infected cells
ALT Elevated Elevated  9 N antigens (N1-N9)
 Hepatitis D virus (HDV)  Human infections occur with N1 and N2
- Delta virus  Antigenic variation
- Requires infection with Hepatitis B Antigenic drift Antigenic shift
- Route of transmission is same as HBV Caused by RNA replication errors of Drastic change in
- Can occur as coinfection or superinfection the virus surface antigen
- HDAg found early, disappears rapidly, not very A minor change in antigenic resulting in a new
useful structure as mutation accumulate H or B antigen
- IgM anti-D and total anti-HD (IgM and IgG) Occurs in all types of influenza
detected during acute phase  Mechanisms of antigenic shift

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 - Genetic reassortment of the eight ssRNA strands  Spread through respiratory secretions
of two separate influenza virus (aerosol, direct contact)
 Pigs have receptors for both avian and human - Specimen
influenza viruses as well as swine influenza  Aspirated secretions
viruses and can be co-infected when the  Nasopharyngeal washes
genome of both influenza viruses become - Test
mixed onto a single virion, resulting into a  IF
new strain  EIA
- Adaptive mutation in which a novel virus slowly  Mumps virus
adjust and becomes transmissible from a - Classified in the genus Rubulavirus
mammalian host - HN and F surface antigen
 Antigenic shift is associated with influenza A - Causes acute illness producing unilateral or
bilateral swelling of parotid glands
- Testes, ovaries, and pancreas can also be infected
- Mode of transmission
 Spread by droplets of infected saliva
- Specimen
 Infected saliva
 Urine
 CSF
- Test
 IF
 EIA
- Viral isolation
 Vero or LLC-MMK 2 cells
 Measles virus
- Classified in the genus Morbillivirus
- Replicates initially in the mucosal cells of the
 Mode of transmission respiratory tract then replicates in the local lymph
- Influenza viruses are spread by aerosols and
nodes, spreads systematically
attack the ciliated epithelial cells lining the - The virus circulates in the T and B cells and
respiratory tract, causing necrosis and sloughing monocytes until the lungs, gut, bile duct, bladder,
of the cell skin, and lymphatic organs
- Koplik’s spots
Paramyxoviridae
 Lesions on the oral mucosa consisting of
 Helical capsid with envelope irregular red spots with a bluish-white speck
 Non-segmented in the center and appear usually 2-3 days
 Includes several genera before the rash and are diagnostic
- Morbilivirus - Complications
- Paramyxovirus  Otitis, pneumonia, and encephalitis
- Pneumovirus - Mode of transmission
- Rubulavirus  Spreads by aerosols
 Parainfluenza virus (PIV) - Specimen
- PIV 1-4 cause disease to humans  Nasopharynx
- Major cause of respiratory disease in young  Urine
children - Test
- PIVs 1 and 2 cause the most illnesses in children  EIA
between 2 and 4 years of age  IF
- PIV-1 – primary cause of croup  Neutralization
(laryngotracheobronchitis) in children  Measles-specific IgM-acute phase
- PIV-3 – causes bronchiolitis and pneumoniae in - Grows on PMK cells – formation of distinctive
infants spindle shape or multinucleated cells
- PIV-4 – generally causes mild upper respiratory  Respiratory syncytial virus (RSV)
tract infection - Member of the genus Pneumovirus
- PIV surface antigen - The most common virus isolated from infants with
 HN (hemagglutinin-neuramidase) – viral lower respiratory tract infection
adhesion molecule - Causes croup, bronchitis, bronchiolitis or
 F (fusion) – responsible for the fusion of the interstitial pneumonia
virus to the cell and of one infected cell to - No vaccine is available
another infected cell
- Mode of transmission - Mode of transmission

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  Spreads mostly through large-particle  Sexual
droplets and contact with fomies rather than  Parenteral
through inhalation of small particles  Horizontal
o Spread of an infectious agent from one
- Specimen
individual to another, usually through
 Nasopharyngeal swabs and washes
contact with bodily excretions or fluids,
- Test
such as sputum or blood, that contain the
 DFA
agent
 EIA
 Vertical
 Human metapneumovirus
o Passage of a disease-causing agent
- First described in children with previously virus-
(pathogen) from mother to baby during
negative cultures
the period immediately before and after
- Symptoms similar to infections caused by the RSV,
birth
influenza virus and parainfluenza virus
o Transmission might occur across the
placenta, in the breast milk, or through
Picornaviridae
direct contact during or after birth
 One of the smallest
- HIV tropism
 Icosahedral capsid
 Naked virus
 Enterovirus
- Acid-resistant
- Smallest RNA virus
- Polioviruses 1-3
- Coxsackievirus A1-23
 Herpangia
 Hand, foot, mouth disease
- Coxsackievirus B1-6
 Myocarditis
- Enteroviruses 68-72  HIV’s receptor is for CD4 and both T cells and
monocytes have it
 70 can cause acute hemorrhagic conjunctivitis
 HIV needs CCR5 and/or CXCR4 to bind to the
 Hepatitis A
- Echoviruses 1-32 cells
- Virulence factors
- Parechovirus 1-4
 Envelope glycoproteins (gp120, gp41)
 Rhinovirus
 Reverse transcriptase (p64)
- Acid-sensitive
 Protease (p10)
- Major cause of common cold
 Integrase (p32)
- Transmission through aerosols, contact with
- Primary infection
fomites, and secretion
 Aseptic meningoencephalitis is the most
common neurologic manifestation
Retroviridae
 Often asymptomatic
 Icosahedral with envelope
 Nonspecific symptoms of an acute viral illness
 Reverse transcriptase may be observed
 Subfamilies include Oncovirinae (tumor, cancer cell)  Symptoms usually begin 2 weeks after
and Lentivirinae (HIV) exposure and infection resolves in 3-4 weeks
 HIV - Chronic infection
 Prolonged asymptomatic phase
 Ongoing viral replication and CD4 depletion
 Fatigue, lymphadenopathy, weight loss, night
sweats and other systemic manifestations
- Acquired immune deficiency syndrome (AIDS)
 CD4 <200 cells/mm3
 Opportunistic infections and reactivation of
latent infections become more common

- Mode of transmission - Pathogenesis

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  The virus remains for a week at the trauma
site where it multiplies
- Virion enters peripheral nervous system
- Passive ascent via sensory fibers
- Replication in dorsal ganglion
- Rapid ascent in spinal cord
- Descending infection via nervous system to eye,
salivary glands, skin and other organs
- Infection of spinal cord, brain stem, cerebellum,
and other brain structures
Infection with the virus typically begins when an
infected animal’s saliva enters a puncture site
 Progression of rabies disease
- Incubation phase
 Asymptomatic
 60-365 days after bite
 Viral status
o Low titer
o Virus in muscle
- Prodrome phase
 Fever, nausea, vomiting, loss of appetite,
headache, lethargy, pain at site of bite
 2-19 days
 Viral status
o Low titer
o Virus in CNS and brain
- Neurologic phase
 Hydrophobia, pharyngeal spasm,
hyperactivity, anxiety, depression, CNS
 HIV leads to low levels of CD4 T cells
symptoms, loss of coordination
 Direct viral killing of infected cells
 Paralysis, confusion, delirium
 Increased susceptibility to the induction of
 2-7 days
apoptosis in infected cells
 Viral status
 Killing of infected CD4 T cells by CD8
o High titer
cytotoxic lymphocytes that recognize viral
o Virus in both brain and other sites
peptides
 Immunologic status
 When CD4 T cell numbers decline below a
o Detachable antibody in serum and CNS
critical level, cell-mediated immunity is lost,
- Comatose
and infections with a variety of opportunistic
 Coma, hypotension, hypoventilation,
microbes appear
secondary infections, cardiac arrest
 HTLV 1 – T cell leukemia and lymphoma
 0-14 days
 HTLV 2 – no known diseases associated;
 Viral status
increased in drug abuse and hairy cell
o High titer
leukemia
o Virus in both brain and other sites
- Death
Rhabdoviridae
 Forms of rabies
 Rabies virus is the most significant pathogen
- Furious
 Zoonotic infection spread from animals to human  The first acute signs of neurological
 Primary reservoir – canines, skunks, raccoons, involvement are periods of agitation,
badgers, cats, bats disorientation, seizures, and twitching
 Principal reservoir – dogs  Spasms in the neck and pharyngeal muscles
 Mode of transmission lead to severe pain upon swallowing. As a
- Through bites and scratches (with saliva) result, attempts to swallow or even the sight
- Through inhalation of aerosolized virus of liquids bring on hydrophobia
- Transplantation of infected tissue  At this phase, the patient is fully coherent and
 Pathogenesis alert
- Virus inoculated - Dumb
 Infection with the virus typically begins when  A patient is not hyperactive but paralyzed,
an infected animal’s saliva enters a puncture disoriented and stuporous
site - Both forms progress to the coma phase, resulting
- Virus replication in muscle in death from cardiac or respiratory arrest

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 Laboratory diagnosis
- Oftenly, disease is diagnosed at autopsy
- Criteria indicative of rabies are intracellular
inclusions (Negri bodies) in nervous tissue
- Rbies can also be grown in cell culture
- Inoculated cell cultures or brain tissues are
subsequently examined with direct
immunofluorescence
- Rabies antibody titers in serum and cerebrospinal
fluid are usually measured by ELISA
 Prevention and control
- The first protective measure is local treatment of
the wound
 The wound should be scrupulously washed
with soap or detergent and water, followed by
debridement and application of an antiseptic
such as alcohol or peroxide
- Post-exposure immunization
 Initially, the wound is infused with human
rabies immune globulin (HRIG) to impede
the spread of virus and is also injected
intramuscularly to provide immediate
systemic protection
 A full course of vaccine, the human diploid
cell vaccine (HDCV) is started
simultaneously
 Vaccination entails intramuscular
intradermal injection on the day of exposure
then on the 3 rd, 7th, 14th, 28th, and 60th days,
with two boosters
Epidemiology of Alphavirus and Flavivirus Infection
 Disease/Viral factors
- Enveloped virus must stay wet and can be
inactivated by drying, soap, and detergents
- Virus can infect mammals, birds, reptiles and
insects
- Asymptomatic or nonspecific (fluke fever or
chills), encephalitis, hemorrhagic fever, or
arthritis
 Transmission
- Specific arthropods of each virus (zoonosis;
arbovirus)
 Risk
- People who enter ecologic niche of arthropods
infected by arboviruses
 Geography/Season
- Endemic regions for each arbovirus are
determined by habitat of mosquito or other vector
- Aedes mosquito, which carried dengue and yellow
fever, is found in urban areas and in ponds of
water
- Culex mosquito, which carries St. Louis
encephalitis and West Nile encephalitis viruses, is
found in forest and urban areas
- Disease is more common in summer
 Modes of control
- Mosquito breeding sites and mosquitoes should
be eliminated
- Live attenuated yellow fever virus and inactivated
Japanese encephalitis virus vaccines
Togaviridae
 Icosahedral capsid
 Envelope
 Resembles mRNA
 Classifications
- Alphavirus
- Rubivirus
- Artevirus
 Rubella
- German measles
- Humans are the only reservoirs
- Mild exanthematous disease (child and adult)
- Congenital rubella syndrome (pregnant)
- Spread through air droplets
 Alphavirus (arbovirus)
- Sindbis
 Vector – Aedes and other mosquitos
 Host – birds
 Distribution – Africa, Australia, India
 Disease – subclinical
- Semliki forest
 Vector – Aedes and other mosquitos
or  Host – birds
 Distribution – East and West Africa
 Disease – subclinical
- Venezuelan equine encephalitis (VEE)
 Vector – Aedes, Culex, Psophora
 Host – rodents, horses
 Distribution – North, South, and Central
America
 Disease – mild systemic; severe encephalitis
 Mosquito-borne viral disease that produces
primarily an undifferentiated febrile illness in
humans and encephalitis in equine
 First recognized in Venezuela in 1938
 Primary affects all equine species (horses,
donkeys, mules, zebras)
 Humans can also contract VEE
 Zoonotic reservoir – bats, birds, rodents,
equines, certain tropical jungle mammals
 Horses are the most important amplifier hosts
in large epidemic outbreaks
 VEE in equines
o Symptoms include high fever, depression,
diarrhea, anorexia, and weight loss
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 o In nonfatal cases, fever subsides and - Transmitted to humans through the bite of
convalescence is protracted infected Culex species mosquitoes, particularly
o In fatal cases, fever persists and the horse Culex tritaeniorhynchus
loses balance that show a distinctive lack  Dengue virus
of coordination that leads to a “leaning - Vector – Aedes
stance” and circling due to the swelling of - Host – humans, monkeys
the brain and consequently dies within 2- - Distribution – worldwide, especially tropics
4 days - Disease – mild systemic; breakbone fever, dengue
- Eastern equine encephalitis hemorrhagic fever, and dengue shock syndrome
 Vector – Aedes, Culiseta - Serotypes 1-4
 Host – birds - Also called breakbone fever because of the
 Distribution – North and South America, severe pain induces in the muscles and joints
Carribean - Dengue fever
 Disease – mild systemic; encephalitis  Characterized by fever and rash (petechiae in
- Western equine encephalitis (WEE) tourniquet)
 Vector – Culex, Culiseta  Can cause dengue hemorrhagic fever (DHF)
 Host – birds (natural); horses and humans and dengue shock syndrome (DSS)
(accidental)  Yellow fever virus
 Distribution – North and South America - Vector – Aedes
 Disease – mild systemic; encephalitis - Host – human, monkeys
 Isolated from the brains of affected horses - Distribution – Africa, South America
when an epizootic occurred in San Joaquin - Disease – hepatitis, hemorrhagic fever
Valley of California in summer of 1930 - Severe systemic disease
 In 1938, WEE was recovered from the brain of  Degeneration of liver, kidney, and heart
a child with fatal encephalitis - Hepatitis (jaundice)
 Widely distributed in the western plains and - Hemorrhagic fever
valleys of the US, Canada, and South America - Massive gastrointestinal hemorrhages (black
 Culex tarsalis is the principal vector vomit)
 Ae. melanimon and Ae. dorsalis are also  St. Louis encephalitis virus
competent vectors - Vector – Culex
- Chikungunya - Host – birds
 Vector – Aedes - Distribution – North America
 Host – humans, monkeys - Disease – encephalitis
 Distribution – Africa, Asia  West Nile virus
 Disease – fever, arthralgia, arthritis - Vector – Culex
 Swahili for “that which bends up” - Host – birds
 Crippling arthritis associated with serious - Distribution – Africa, Europe, Central Asia, North
disease America
- Disease – fever, encephalitis, hepatitis
Flaviviridae  Russian spring-summer encephalitis
 Icosahedral capsid - Vector – Ixodes and Dermacetor ticks
 Enveloped - Host – birds
 Zoonotic infection - Distribution – Russia
 Arboviruses - Disease – encephalitis
 Japanese encephalitis virus  Powassan encephalitis
- Vector – Culex - Vector – Ixodes ticks
- Host – pigs, birds - Host – small mammals
- Distribution – Asia - Distribution – North America
- Disease – encephalitis - Disease – encephalitis
- The virus is maintained in a cycle between  Hepatitis C
mosquitoes and vertebrate hosts, primarily pigs
and wading birds Disease Mechanisms of Togaviruses and Flaviviruses
 Uninfected mosquitoes bite pigs and  Cytolytic, except for rubella and hepatitis C
waterbirds infected by JE  Establish viremia and systemic infection
 Infected mosquito transmit virus to humans  Good inducers of interferon and cytokines, which can
 Infected mosquito transmit virus to account for the flulike symptoms during prodrome
vertebrates  Arboviruses, except for rubella and hepatitis C
- Humans are incidental or dead-end hosts, because  Flaviviruses can infect cells of the monocyte-
they usually do not develop high enough macrophage lineage
concentrations of the virus in their bloodstreams
to infect feeding mosquitoes
dane.
 Non-neutralizing antibody can enhance flavivirus o Less vigorous CTL response in the
infection via Fc receptors on cells immune system, and thus can ultimately
Flulike Encephalitis persist in the host organism immediately
syndrome o Chronic LCMV infection
Dengue +  Lassa virus
Yellow fever + - Acquired primarily by contact with excretions
St. Louis from multimammate rat (Mastomys natalensis)
+ + - Mode of transmission
encephalitis
West Nile  Inhalation of aerosolized virus
+ +  Direct contact through breaks in the skin
encephalitis
Venezuelan  From person to person
+ +
encephalitis
Western equine Bunyaviridae
encephalitis
+ +  Segmented helical capsid
Eastern equine  Enveloped
+ +  Epidemiology
encephalitis
Japanese - Disease/Viral factors
+ +  Virus is able to replicate in mammalian and
encephalitis
arthropod cells
Hepatitis Hemorrhage Shock  Virus is able to pass into ovary and infect
Dengue + + + arthropod eggs, allowing virus to survive
Yellow during winter
+ + + - Transmission
fever
 Through arthropods blood meal – California
encephalitis group, Aedes mosquito
Arenaviridae
 Aedes mosquitoes are aggressive daytime
 Helical capsid
feeders and live in forests
 Pleomorphic envelope
 Aedes mosquitoes lay eggs in small pools of
 Latin word “arena” means sand water trapped in places such as trees and tires
- Sandy and granular appearance in electron  Hantavirus is transmitted in aerosols from
microscope rodent urine and by close contact with
Old world New world infected rodents
LCMV Tacaribe - Risk
Lassa virus Guanarito  People in habitat of arthropod or rodent
Junin vector
Machupo  California encephalitis group – campers,
 Rodent-borne forest rangers, woodsmen
 Infects rodents and humans - Geography/Season
 Mode of transmission  Disease incidence correlates with distribution
- Inhalation if aerosolized of vector
- Contact with fomites  More common in summer
 LCM virus - Modes of control
- Causes an influenza-like virus  Elimination of vector or vector’s habitat
- About 25% of infected patients develop meningitis  Avoidance of vector’s habitat
- Two strains  Includes the genera Orthobunyavirus, Phlebovirus, and
 Armstrong strain Nairovirus classified as arbovituses
o Original, parent virus  Replicate initially in the gut of the arthropod vector
o Originated from the brain and was  Rift valley fever, La Crosse, California encephalitis, and
isolated by Charles Armstrong in 1934 the Crimean-Congo hemorrhagic fever
o Triggers a vigorous cytotoxic T  Bunyaviruses
lymphocytes (CTL) response and thus, it Virus Vector Disease
is cleared rapidly by the host Bunyavirus (49 Mosquito Febrile illness,
o Acute LCMV infections species) encephalitis,
 Clone 13  Bunyamwera febrile rash
o Variant from the parent virus virus
o Isolated from the spleen and is  California
consequently tropic for visceral organs encephalitis
o First isolated from mice which sustained virus
a persistent LCMV infection from birth  La Crosse virus
 Oropouche virus

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Hantavirus (22 None Hemorrhagic  Cold-like infection in adult
species) fever with renal  Pediatric diarrhea
syndrome, adult  SARS
respiratory  MERS-CoV
distress  SARS-CoV 2
syndrome
Sin Nombre virus None Hantavirus Filoviridae
pulmonary shock,  Filamentous
pulmonary  Helical capsid
edema  Enveloped
Nairovirus (6 Tick Sandfly fever,  Rarely cause infection but high mortality rate
species) hemorrhagic  Marburg virus
 Crimean-Congo fever, - Hemorrhagic fever virus
hemorrhagic encephalitis, - Filamentous, enveloped, negative-strand RNA
fever virus conjunctivitis, viruses that may appear in the shape of a
myositis shepherd’s crook or in the shape “U” or “6”
Phlebovirus (9 Fly Hemorrhagic - May be coiled, toroid or branched
species) fever - Endemic in Africa but was first described in
 Rift valley fever Germany during small epidemics in the 1960s
virus - Mode of transmission
 Sandfly fever  Grivet (Chlorocebus aethiops)
virus  Egyptian rousette (Rousettus aegyptiacus)
 Hantavirus  May be endemic in bats or wild monkeys and
- Rodent-borne can be spread to humans and between
- Causative agent of the zoonotic diseases humans
hantavirus pulmonary syndrome (HPS) and  Contact with the animal reservoir or direct
hemorrhagic fecer with renal syndrome (HFRS) contact with infected blood or secretions can
- Hantaanvirus spread the disease
- Seoul virus  Transmitted by accidental injection and
- Puumala virus – mild form of HFRS through use of contaminated syringes
(nephrophatia hemorrhagica) - Epidemiology
- Dobrava virus  The first identification of MBGV occurred
 Sin Nombre during an outbreak in Germany and Serbia in
- “No name” 1967, almost a decade before the discovery of
- Hantavirus with pulmonary syndrome (HPS) Ebola virus (EBOV)
- Mode of transmission  The source of primary infection during this
 Inhalation through aerosolized mouse urine, outbreak was exposure to tissues and blood
saliva, and feces from African green monkeys imported from
 Direct contact with feces, urine, saliva of Uganda for use in the pharmaceutical industry
infected rodents  Although the first outbreak occurred in
 Bites of rodent hosts Europe, since that time, almost all MBGV cases
have been reported from East Africa, with the
Coronaviridae sources of primary infection presumed to be
 Helical capsid located within 500 miles of Lake Victoria
 Enveloped - Clinical manifestation
 Club shaped projection  Maculopapular rash, petechiae, purpura,
 Longest positive sense RNA virus ecchymoses, and hematomas are typical
 Named for solar corona-like appearance (surface hemorrhagic manifestations
projections) of their virions when viewed with an  Death occurs due to multiple organ
electron telescope dysfunction syndrome (MODS) due to fluid
 Second most prevalent cause of the common cold redistribution, hypotension, disseminated
(first is rhinovirus) intravascular coagulation, and focal tissue
 In 2002, an outbreak of severe acute respiratory necroses
syndrome (SARS) in Guangdong Province, South - Laboratory diagnosis
China, spread to Hong Kong, and then around the  ELISA
world  Antigen detection tests
 Viruses inoculated into the respiratory tracts of  Serum neutralization test
human have been found to infect epithelial cells  RT-PCR assay
 Targets epithelial cells of gastrointestinal tract  Virus isolation by cell culture
 Most likely spread by aerosols and in large droplets

dane.
 - Treatment  Wear appropriate PPEs when taking care of ill
 No specific treatment for Marburg patients
hemorrhagic fever
 Supportive care Caliciviridae
o Maintenance of circulation and blood  Icosahedral capsid
pressure  Naked
o Regulation of fluids and electrolyte levels  Four genera – Sapovirus, Norovirus, Lagovirus, and
in the blood Vesivirus
o Transfusions of blood and blood clotting - Sapovirus (SaVs) and Norovirus (NoVs) –
factors may also be required etiologic agent of human gastroenteritis
 Ebola virus  Hepatitis E
- Filamentous, enveloped, negative-strand RNA  Noroviruses
virus - Causes outbreaks of acute gastroenteritis in
- Family Filoviridae and order Mononegavirale schools, colleges, nursing homes, and families, as
- Causes VHF outbreaks in humans with a case well as on cruise ships
fatality rate up to 90% - Found in drinking water, swimming areas, and
- Derived its name from Ebola river contaminated food
- Five distinct species – Bundibugyo, Sudan, Zaire, - Mode of transmission
Ivory coast, and Reston (found in Philippines)  Foodborne (commonly)
- Reservoir host  Waterborne (significant)
 Fruit bats of Pteropodidae family  Person-person (significant)
- Mode of transmission - Clinical manifestation
 Through close contact with the blood,  Incubation period is 24-48 hours
secretions, organs, or other bodily fluids of  Abrupt onset of severe nausea, vomiting, and
infected animals diarrhea and low grade fever
 Human-to-human transmission – close  Sapovirus
contact with the blood, secretions, organs, or - Diarrheagenic viruses distinguished by a cup-
other bodily fluids of infected people shaped morphology
- Clinical manifestation - Cause diarrhea in infants, young children, and
Symptoms that Symptoms that elderly patients
Time frame occur in most occur in some - Discovered in Sapporo, Japan in 1977
Ebola patients Ebola patients
Within a few days High fever, Sore throat,
of becoming headache, muscle hiccups, rash, red
infected with the ache, stomach and itchy eyes,
virus pain, fatigue, vomiting blood,
diarrhea bloody diarrhea
Within one week Chest pain, shock, Blindness,
of becoming and death bleeding
infected with the
virus
- Laboratory diagnosis
 ELISA
 Antigen detection tests
 Serum neutralization test
 RT-PCR assay
 Virus isolation by cell culture
- Treatment
 Intravenous fluids or oral rehydration with
solutions containing electrolytes
 No specific treatment or vaccine is yet
available for EHF
- Prevention and control
 Avoid contact with wildlife animals
 Avoid eating raw or undercooked animal meat
 Isolate Ebola HF patients from contract with
unprotected persons
 Avoid close physical contact with Ebola
patients
 Wash hands thoroughly after visiting sick
patients
dane.