VIROLOGY

Introduction to Virology
A virus is an obligate intracellular
parasite containing genetic
material surrounded by protein

Virus particles can only be

observed by an electron
microscope
2

 Recognizing the shape, size, and

structure of different viruses is
critical to the study of disease
Viruses have an inner core of
nucleic acid surrounded by protein
coat known as an envelope
Most viruses range in sizes from 20
250 nanometers
3

Viral Properties
Viruses are inert (nucleoprotein )
filterable Agents
Viruses are obligate intracellular
parasites
Viruses cannot make energy or proteins
independent of a host cell
Viral genome are RNA or DNA but not
both.
Viruses have a naked capsid or envelope
with attached proteins
Viruses do not have the genetic
4
capability to multiply by division.

VIRAL STRUCTURE SOME

TERMINOLOGY

virus particle = virion

protein which coats the
genome = capsid
capsid usually symmetrical
capsid + genome =
nucleocapsid
may have an envelope
5

Virion
The complete
infectious unit
of virus
particle
Structurally
mature,
extracellular
virus particles.
9

 HOST RESISTANCE TO VIRAL INFECTION

Primary Defenses
Skin barrier (dead keratinized cells impervious to viruses)
Skin has acids and other inhibitors produced by normal
bacterial flora
Mucociliary elevator

Immune Defense
Innate immune response
Interferon
Complement
Natural killer cells

Adaptive immune response

Antibody
Cytotoxic T lymphocytes

 Interferons (IFNs) are a family of eukaryotic cell proteins

classified according to the cell of origin. IFN-alpha and IFNbeta are produced by a variety of virus-infected cells. They:
first described in 1957 byAlick IsaacsandJean Lindenmannat
theNational Institute for Medical Researchin London
Act on target cells to inhibit viral replication.
Do not act directly on the virus.
Are not virus-specific.
Are species-specific (e.g., mouse IFN versus human IFN).

Interferon inhibits viral protein synthesis

Through activation of an RNA endonuclease, which digests viral
RNA.
By activation (by phosphorylation) of protein kinase that
inactivates eIF2, inhibiting viral protein synthesis.
Exogenous human IFN (produced by recombinant DNA
technology) may be used in
antiviral therapy for chronic, active HBV and HCV infections.

DNA VIRUSES: CHARACTERISTICS

All DNA viruses:
Are double-stranded, except
parvovirus
Are icosahedral, except poxviruses,
which are a brick-shaped "complex"
Replicate their DNA in the nucleus,
except poxvirus

PARVOVIRIDAE
Virus Characteristics
ssDNA virus, linear
Naked, icosahedral

Viruses of Medical Importance--B 19

Reservoir-human respiratory tract
Transmission respiratory route, formites,
vertical transmission
tr-

 Diseases
Children/adults
Fifth disease, erythema infectiosum, slapped cheek fever
7-1 0 day incubation
Nonspecific "flu-like" symptoms followed by raised, indurated
facial rash
Rash and arthralgias (adults predominantly) are due to
immune complexes in the skin and joints
Fetus

Severe anemia
Congestive heart failure
Hydrops fetalis
Spontaneous abortion

Diagnosis--serology and molecular analysis

Treatment--supportive care

PAPILLOMAVIRIDAE
Virus Characteristics
dsDNA virus, circular
Naked, icosahedral

Viruses of Medical Importance

Human papilloma virus (HPV)

Reservoir--human skin and genitals

Transmission--direct contact, fomites
Pathogenesis
Virus infects basal layer of the skin and mucous
membranes
Hyperkeratosis leads to the formation of the
"wart"
Malignancy may result: E6 and E7 inhibit tumorsuppressor genes p53 and Rb, respectively.

 Diseases
Cutaneous warts
Anogenital warts (Condylomata acuminata)

Diagnosis
Cutaneousclinical grounds
Genital--finding of koilocytic cells (cells with perinuclear
cytoplasmic vacuolization and nuclear enlargement) in Pap smears
In situ DNA probes and PCR

Treatment
Cryotherapy, electrocautery, or chemical means (salicylic acid)
Imiquimod (induces proinflammatory cytokines), interferon-a,
and virus specific cidofovir

Prevention
A vaccine composed of HPV capsid proteins produced by
recombinant DNA technology
Safe sex practices

POLYOMAVIRIDAE

ADENOVIRIDAE
Reservoir-ubiquitous in humans and animals
Transmission--respiratory, fecal-oral, direct contact
Disease

Acute respiratory disease (ARD) and pneumonia

Pharyngoconjunctivitis
Epidemic keratoconjunctivitis
Acute hemorrhagic cystitis

Diagnosis--serology; ELISA
Treatment---supportive care
Prevention--live, nonattenuated vaccine

HERPESVIRIDAE
Virus Characteristics

Large dsDNA
Enveloped, icosahedral
Derives envelope from nuclear membrane
Intranuclear inclusion bodies
Establishes latency

Viruses of Medical Importance

Herpes simplex virus 1 and 2 (HSV)
Varicella-zoster virus (VZV)
Epstein-Barr virus (EBV)

Cytomegalovirus ( CMV)

POXVIRIDAE
Virus Characteristics

Large dsDNA, enveloped

Complex morphology
Replicates in the cytoplasm
Potential biowarfare agent

Viruses of Medical Importance

Variola
Vaccinia (vaccine strain)
Molluscum contagiosum

Smallpox/Variola
Reservoir: Humans
Variola has I serotype,
Transmission----respiratory route
Pathogenesis
Via inhalation, the virus enters the upper respiratory tract and disseminates via
lymphatics --viremia
After a secondary viremia, the virus infects all dermal tissues and internal organs
Classic "pocks"

Disease
5-1 7 day incubation
Prodrome of flu-like illness for 2-4 days
Prodrome followed by rash, which begins in the mouth and spreads to the face,
arms and legs, hands, and feet and can cover the entire body within 24 hours
All vesicles are in the same stage of development (synchronous rash)
Diagnosis
Clinical
Guarnieri bodies found in infected cells (intracytoplasmic
Treatment : Supportive

Molluscum contagiosum
Reservoir--humans
Transmission-direct contact (sexual) and fomites
Pathogenesis--replication in dermis
Disease
Single or multiple ( <20) benign, wart-like tumors
Molluscum bodies in central caseous material ( eosinophilic
cytoplasmic
inclusion bodies)
Diagnosis
Clinical (warts are umbilicated)
Eosinophilic cytoplasmic inclusion bodies
Treatment
In healthy persons, self limiting
Ritonavir, cidofovir in immunocompromised

RNA VIRUSES: CHARACTERISTICS

All RNA viruses are single stranded (ss), except Reovirus.
ss(-)RNA viruses carry RNA-dependent RNA polymerase.

A virion-associated polymerase is also carried by:

Reovirus
- Arenavirus
- Retrovirus (reverse transcriptase)

Most are enveloped; the only naked ones are:

Picornavirus
Calicivirus and Hepevirus
Reovirus

Some are segmented (different genes on different pieces of RNA)

Reovirus
Orthomyxovirus
Bunyavirus
Arena virus

CALICIVIRIDAE
Norwalk Virus
Reservoir--human gastrointestinal tract
Transmission--fecal-oral route, contaminated food
and water
Disease-- acute gastroenteritis
Diagnosis RIA, ELISA
Treatment
No specific antiviral treatment
Self-limiting
Prevention-handwashing

PICORNAVIRIDAE

FLAVIVIRIDAE

TOGAVIRIDAE

CORONAVIRIDAE
Coronavirus
Second most common cause of the
common cold
Winter/spring peak incidence

 SARS-CoV
Reservoir--birds and small mammals (civet cats)
Transmission
Respiratory droplets
Virus is also found in urine, sweat, and feces

Disease--severe acute respiratory syndrome (SARS)

Atypical pneumonia
Clinical case definition includes: fever of > 1 00.4F, flu-like illness, dry
cough, dyspnea, and progressive hypoxia
Chest x-ray may show patchy distribution of focal interstitial infiltrates
Diagnosis
Includes clinical presentation and prior history of travel to endemic area or
an association with someone who recently traveled to endemic area

Lab tests: detection of antibodies to SARS-CoV, RT-PCR, and isolation of

the virus in culture
Treatment
Supportive
Ribavirin and interferon are promising

RETROVIRIDAE

Family Characteristics
Positive-sense ssRNA
Virion-associated reverse transcriptase
Enveloped

Viruses of Medical Importance

Oncovirus group
Human T-cell leukemia/lymphotropic (HTLV)
Adult T-cell leukemia
C-type particle

Lentivirus group-human immunodeficiency virus

(HIV); acquired immunodeficiencysyndrome

Human Immunodeficiency Virus

(HIV)

STAGE OF
ILLNESS

Acute
Windo
retroviral
w
Syndrom
Period
e

HIV
positiv
e
HIV positive
asymp symptomatic
tomati phase
c
phase

AIDS

AIDS defining
illness,
Opportunistic
infections,
wasting
syndrome,
dementia
positive

Fever, skin
rash

Nil

Nil

Prolonged fever,
recurrent
common
infections, TB,
diarrhoea,
Generalized
lymphadenopathy

Onset

Within 2 -4
weeks of
infection

From time
of getting
HIV
infected

6-12
weeks
after HIV
infection

About 2-5 years

after HIV infection

5-10 years after

getting HIV
infection

Diagnosis

PCR Antigen
test

PCR or P
24 antigen
test

3 ELISA
or 1 WB
& 1 ELISA

2 ELISA and 2 major

symptoms

2 ELISA and AIDS

defining illness

Symptoms

HIV test:
ELISA/WB

PARAMYXOVIRIDAE

Family Characteristics
Enveloped, helical nucleocapsid
Negative-sense ssRNA
Viruses of Medical Importance
Measles
Mumps
Parainfluenza
Respiratory syncytial virus (RSV)
Human metapneumovirus (human
MNV)

Measles Virus

Reservoir-human respiratory tract

Transmission--respiratory route
Pathogenesis
Ability to cause cell:cell fusion giant cells
Virus can escape immune detection

Disease
Measles
Presentation generally the 3 C's (cough, coryza, and
conjunctivitis) with photophobia
Koplik spots maculopapular rash from the ears down giant cell
pneumonia (Warthin-Finkeldey cells)

Subacute sclerosing panencephalitis

Rare late complication
- Defective measles virus persists in brain, acts as slow virus
Chronic CNS degeneration

Mumps Virus

Reservoir-human respiratory tract

Transmission-person to person via respiratory
droplets
Pathogenesis--lytic infection of epithelial cells
of upper respiratory tract and parotid glands
spread throughout body.
Disease:
mumps
Asymptomatic to bilateral parotitis with fever,
headache, and malaise
Complications include pancreatitis, orchitis
(leads to sterility in males), and
meningoencephalitis

RHABDOVIRIDAE

Family Characteristics
Negative-sense ssRNA
Bullet shaped
Enveloped, helical

Rabies Virus
Reservoir
In the U.S., most cases sylvatic: bats, raccoons, foxes, and skunks
Worldwide, dogs are primary reservoir
Transmission--bite or contact with a rabid animal
Pathogenesis
After contact, virus binds to peripheral nerves by binding to nicotinic
acetylcholine receptor or indirectly into the muscle at the site of
inoculation
Virus travels by retrograde axoplasmic transport to dorsal root
ganglia and spinal cord
Once virus gains access to spinal cord, brain becomes rapidly
infected

 Disease--rabies
Nonspecific flu-like illness followed by neurologic symptoms of hydrophobia,
seizures, disorientation, hallucination, coma, and death
With rare exception, rabies fatal unless treated by immunoprophylaxis

Diagnosis
Clinical
Negri bodies, intracytoplasmic inclusion bodies (brain biopsy)
DFA (impression smears of corneal epithelial cells), PCR (usually too late)

Treatment
If symptoms are evident: none
If suspect:
Post exposure prophylaxis
One dose of human rabies immunoglobulin (hRIG)
- Five doses of rabies vaccine (day of, 3, 7, 14, 28)
- Killed virus vaccine

Prevention
Vaccine for high-risk individuals
Vaccination program for domestic animals

ORTHOMYXOVIRI DAE

Family Characteristics
Negative-sense ssRNA
Enveloped
Segmented (8 segments)
Helical

Viruses of Medical Importance

Influenza A
Influenza B

Influenza Virus

Distinguishing Features
Envelope contains two glycoproteins, H and N
Used to serotype virus

Reservoir
Influenza A (birds, pigs, humans)
Influenza B (humans only)

Transmission
Direct contact
Respiratory
1997 H5N1 strain jumped directly from birds to humans
2009 H1N1 strain-quadruple reassortment virus (North
American swine, avian, human; Asian and European swine)

 Disease--influenza

Headache and malaise

Fever, chills, myalgias, anorexia
Bronchiolitis, croup, otitis media, vomiting (younger children)
Pneumonia/secondary bacterial infections
Can lead to Reye syndrome or Guillain-Barre syndrome

Diagnosis
Rapid tests (serology)
Clinical symptoms plus season

Treatment
Amantadine/rimantadine (current isolates are commonly resistant)
- Inhibit viral uncoating
- Administer orally

Zanamivir/oseltamivir
Neuraminidase inhibitors
Zanamivir is inhaled
Oseltamivir is given orally

VIRAL HEPATITIS

THANK
YOU