Medical Virology  No metabolic needs-do not eat, respire,

Introduction to Basics move, grow etc.

What are Viruses?  They can be crystallized and stored in
bottles like chemicals
Viruses are obligate intracellular parasites
containing genetic material surrounded by Because viruses contain both living and non-
protein living characteristics they are considered to be
transitional between life and non-life
Viruses vary considerably in size (0.02 µm-0.3
µm) and shape Viral Structure
 Smallpox viruses are among the largest Nucleic acid core (DNA or RNA) surrounded by
viruses proteins
 Polio viruses are among the smallest The nucleic acid portion known as genome
Virus particles can only be observed by an The genome of virus is surrounded by a protein
electron microscope coat known as a capsid which is formed from a
number of individual protein molecules called
General Characteristics of Viruses
capsomeres
Viruses show the following features:
Capsomeres are arranged in a precise and highly
 they are filterable agents repetitive pattern around nucleic acid

 cannot be seen with light microscope-only Capsid usually symmetrical

electron microscope
Capsid + genome = nucleocapsid
 metabolically inert-cannot make energy or
• Envelope: some viruses have this additional
proteins independent of a host cell
surrounding lipid bilayer membrane
 obligate intracellular parasites
• Virion: a complete virus particle
 multiply inside the living cells using host (extracellular)
cell machinery
• Naked: viruses with a nucleocapsid and no
 Not sensitive to antibiotics envelope

Viruses as Living Things • Spikes: projections that extend from viral

envelope that may aid in attachment to the
 Occur in different strains host cell
 Have their own genetic material • Glycoprotein: these surface projections
 Able to mutate serve to attach virions to specific receptor
sites on susceptible host cell surfaces
 Able to reproduce (within host cell only)
Functions of viral components
 Cause infectious disease
• Nucleic acids
 Get destroyed by ultra violet rays
• Help viruses to replicate themselves in host
Viruses as Non-Living Things cells
 They lack cellular structure i.e. not made of Capsids
cells
• protect nucleic acid core from inactivation  Examples: influenza virus, rabies virus
by nucleases
Complex
• play a role in the introduction of viral
genome into host by adsorbing on the host  Have a combination of icosahedral and
cell surface helical shape and may have a complex outer
wall or head-tail morphology
Envelope
 The head-tail morphology structure is
• Helps to protect viruses from drying
unique to viruses that only infect bacteria
(enhances transmission)
and are known as bacteriophages. The head
• Helps to attach to host cell membrane of the virus has an icosahedral shape with a
helical shaped tail
• Makes virus susceptible to chemical agents
that dissolve lipids  An example is Poxvirus

Viral shapes Enveloped

Viruses are of different shapes  This virus structure is a conventional
icosahedral or helical structure that is
They are:
surrounded by a lipid bilayer membrane,
 rod shaped meaning virus is encased or enveloped

 spherical  Examples are influenza virus, Hepatitis C

virus and HIV
 bullet shaped
Classification
 filament shaped
Based on genome replication
 icosahedral shaped
The Baltimore Classification System
 tadpole shaped
Class I viruses: double-stranded DNA genome
Classification
 The genome is double stranded DNA so
 Based on morphology mRNA is synthesized in the normal fashion
Icosahedral using negative-strand DNA as a template

 The icosahedron is made up of equilateral  Examples: Adenoviruses

triangles fused together in a spherical shape Class II viruses: single-stranded DNA genome
 The genetic material is fully enclosed inside  The genome is single-stranded DNA. Form a
capsid ds DNA intermediate during replication and
 Examples: polioviruses, rhinoviruses and this intermediate is used for transcription
adenovirus  Examples: Parvovirus
Helical Class III viruses: ds RNA genome
 Virus has its capsid shaped into a rod-shaped  genome is ds RNA. One strand of which is
structure therefore equivalent to mRNA
 This type of shape has a central cavity that  Examples: Reoviruses, rotavirus
encloses its nucleic acid
Class IV viruses: positive-strand RNA genome • Uncoating (eclipse)
 genome is single-stranded RNA that can • Biosynthesis
serve as mRNA directly
 transcription of mRNA from viral nucleic
 Example(s): Poliovirus acid
Class V viruses: negative-strand RNA genome  translation of mRNA into early proteins
 genome is ss-RNA that serves as template  replication of viral nucleic acid
for synthesis of viral mRNA
 synthesis of late proteins
 Examples: rabies virus, mumps virus
• Synthesis of viral nucleic acid and protein
Class VI viruses, retroviruses:
• Maturation (assembly)
 genome is positive-strand RNA. This RNA
require reverse transcriptase to copy the • Release
information found in RNA to DNA but it Adsorption (attachment)
expression and replication require synthesis
of a ds DNA molecule  Virus encounters a susceptible host cells

 Example(s): HIV  contact between virion & host cell: by

random collision
Class VII viruses: ds DNA with RNA
intermediate  Interaction between specific proteins on
viral surface and specific receptors on target
 ds-stranded DNA genome that replicate with cell membrane (tropism)
RNA intermediate. Require reverse
transcriptase  Because of the exact fit required, viruses
have a limited host range
 Examples: HBV
 Susceptibility to viral infection depends on
Genetic material present in the virion presence or absence of receptors on cells
Penetration (entry)
 2 mechanisms:
 Endocytosis-called viropexis
 Fusion of virus envelope with membrane
Uncoating
 Release of viral genome
 Cell enzymes (lysosomes) strip off the virus
protein coat

Viral Replication  Virion can no longer be detected; known as

the “eclipse period”
• Adsorption (attachment)
 Eclipse phase lasts until first new virus
• Penetration particle is formed
 Transcription/translation/synthesis  Structural
 DNA viruses:  Nucleic acid synthesis
 Transcription of mRNA from viral DNA  new virus genome
 Translation of mRNA into early proteins  most often by a virus – coded polymerase or
replicase; with some DNA viruses a cell
 early/non-structural proteins are enzymes
enzyme carries this out
which initiate and maintain synthesis of
virus components  Assembly (maturation:
 Replication of viral DNA in host cell  May take place in cell:
nucleus mediated by viral enzymes
 Nucleus (e.g. Herpes & Adenoviruses)
 Synthesis of late/structural proteins required
 Cytoplasm (e.g. Picorna & Poxviruses)
for viral capsid in cytoplasm
 Plasma membrane (most enveloped viruses)
 New viral proteins move to nucleus where
they combine with new DNA to form new  Host cell membrane that becomes envelope
viruses is modified by addition of virus-specific
antigens
 Exception: Poxviruses synthesize their parts
in host cell’s cytoplasm Release:
Transcription/translation/synthesis  Sudden rupture of cells-lysis
 RNA viruses:  Gradual extrusion (budding) of enveloped
viruses through the cell membrane
 “+” sense RNA acts as mRNA-viral proteins
are made immediately in cytoplasm  May occur together with assembly
mediated by viral enzymes
 Not every released virion is infectious
 “-” sense RNA (e.g.) – first makes a “+”
sense RNA copy via viral enzyme
Transcription/translation/synthesis
 Retroviruses (e.g. HIV):
 Contain enzyme “reverse transcriptase”
 “+” sense viral RNA → cDNA → integrated
into host cell chromosome
 mRNA (for viral proteins) and progeny
virion RNA are synthesized from integrated
viral DNA by host cell enzymes (RNA
polymerases)
Synthesis:
 Protein synthesis-2 types
 non-structural (enzymes)
DNA VIRUSES OF MEDICAL
IMPORTANCE Pardon Pa Pa As He Has Pox
DNA Herpesviruses
DNA VIRUSES
• Cause primary and recurrent infections
• Deoxyribonucleic acid (DNA): genetic
material • Infections become more severe with age,
except Poxvirus cancer chemotherapy
• Large, icosahedral, enveloped in
lipoproteins • Most common and serious opportunists
among AIDS patients
• Do not have polymerase enzymes and cause
latent infection Nomenclature of Herpesviridae
First 3 viruses are alpha
Examples of DNA VIRUSES HHV1 = Herpes simplex virus 1 (HSV1) viruses with short
reproductive cycle and
HHV2 = Herpes simplex virus 2 (HSV2)cause mostly skin
infections. They are
HHV3 = Varicella-zoster virus (VZV) latent in sensory neurons
HHV4 = Epstein-Barr virus (EBV) Beta viruses include
HHV5, HHV6, HHV7
HHV5 = Cytomegalovirus (CMV) and they have long
reproductive cycle. latent
HHV6 = Roseola infantum (major cause) in white blood cells .
HHV7 = Roseola infantum (minor cause) Gamma viruses
include HHV4 and
HHV8 = Kaposi sarcoma (KS) HHV8 .
Summary Latent in lymphocytes
HSV-1 &2 and are associated
with cancer
• Both cause painful vesicles on the skin at the
site of inoculation
• HSV-1 causes oro-facial lesions
• HSV-2 causes lesions on the genitalia Bilateral, painful vesicular genital ulcers
Epidemiology HSV1=Oral Herpes
• HSV 1 infection occurs early childhood HSV2=Genital Herpes
• HSV2 is acquired mostly in adulthood Pathogenesis
(predominantly spread by sexual
intercourse)
Transmission
HSV-1:
• Direct contact with mucosa or abraded skin
HSV-2:
• Sexual mode or vertical mode
Latency
• HSV-1: Trigeminal ganglia
• HSV-2: Sacral ganglia Clinical Significance
Skin Infections of Herpes HSV-1
• Herpetic whitlow • Acute gingivostomatitis
• Febrile blisters • Recurrent herpes labialis (cold sores)
• Herpes gladiotorum as seen in wrestlers  Herpetic whitlow
• Eczema herpeticum  Keratoconjunctivitis cornea and conjunctiva affected
• Erythema multiforme  Encephalitis
Herpetic Whitlow HSV-2
• Lesion present on fingers of dentists and  Genital herpes
hospital personnel
 Neonatal herpes (may be caused by HSV-1
• Febrile Blisters as well) Baby passes through infective vaginal secretions.
• Herpetic Gladiotorum  Diagnosis & Treatment
• Seen in athletes/wrestler Diagnosis
 EM, culture
Erythema Multiforme Treatment
Most common associated feature with  Drug of choice = Acyclovir
Erythema Multiforme=HSV
 Acyclovir resistant cases = Foscarnet
Genital Lesions in HSV
Varicella Zoster Virus
• Chickenpox & Shingles  Infection at 16-20 weeks = eye and brain
involvement
• Signs and symptoms
 If mother gets chickenpox after 5 days of
• Chickenpox characterized by lesions on the delivery
back and trunk that spread across body
 No risk to child….
• Shingles lesions localized to skin along an
infected nerve  No need for any prophylaxis
to child
Pathogen
 If mother gets chickenpox before 5 days or
• Varicella-zoster virus (VZV) causes both after 2 days of delivery
diseases
 Child may develop serious neonatal
• Varicella is transmitted by respiratory varicella syndrome
droplet and direct contact
 Prophylaxis should be started immediately
• Zoster not transmitted; it is caused by to both
reactivation of latent virus Varicella for chickenpox
zoster for shingles  V-Z Immunoglobulin
Pathogenesis
 Given within 96 hrs of exposure
 Infected dermal cells cause rash
characteristic of chickenpox  Given to neonates born to chickenpox
mothers:
 Virus becomes latent in nerve ganglia
 If the onset of chickenpox is before 5 days
 Reactivated (VZV) causes shingles or after 2 days of delivery
 The incubation period: 21 days
 Diagnosis & Treatment
 Primary infection is followed by long lasting  Diagnosis
immunity
 EM, culture, serology for IgM Tzanck test can be used for
 Congenital varicella syndrome giant multinucleated cells of
 Treatment the vesicles

 acyclovir, famciclovir
Congenital varicella syndrome (vertical
transmission):  interferon, nucleoside analog of guanosine

 Infants born to mothers who have varicella  live attenuated vaccine

in the first 20 weeks of pregnancy may
 2 doses
develop a congenital infection syndrome
consisting of: limb hypoplasia, muscular  1st dose: at 12-15 months
atrophy, mental retardation and skin scarring
 2nd dose: 4-6 yrs.
Chickenpox in Pregnancy
 Late first trimester or early second trimester
is associated with worst prognosis Epstein-Barr Virus

 Infection at 6-12 weeks = maximum  Causes infectious mononucleosis (IM)-sore

interruption with limb development throat, high fever etc.
 Incubation period:30-50 days Cytomegalovirus
 Transmission: direct oral contact &  Transmitted in saliva, respiratory mucus,
contamination with saliva milk, urine, semen, cervical secretions &
faeces
 Infection begins:
 Commonly latent in various tissues
 In the pharyngeal epithelium, spreads to the
cervical lymph nodes  Most infections are asymptomatic
 then travels via the blood to the liver and Three (3) groups develop a more virulent
spleen form of disease:
 virus remains latent in B cells  foetuses
 reactivation causes B cell Lymphoma and  new-borns
Lymphoproliferative
 immunodeficient adults
EBV ass. Malignancies
Congenital CMV Infections
• Oncogenesis is due to:
• Most new-borns with congenital CMV
• Latent membrane protein-1 are asymptomatic, but as many as 15%
will develop progressive hearing loss
• Viral EBNA-2
Approximately 10% of congenitally infected
• Nasopharyngeal carcinoma
new-borns will show symptoms at birth:
Burkitt’s Lymphoma • Hepatosplenomegaly
• associated with chronic co-infections with • Chorioretinitis
malaria etc.
• Small size for gestational age
Non-Hodgkin lymphoma
• Microcephaly
Hodgkin’s lymphoma
CMV Infections
• Other condition associated is = Hairy cell
Leukemia  Perinatal infection – mostly asymptomatic,
or pneumonitis, & a mononucleosis like
EBV Diagnosis & Treatment syndrome
Diagnosis
 AIDS patients – CMV mononucleosis,
 Agglutination disseminated CMV, retinitis

Treatment  Transplant patients pneumonitis, hepatitis,

myocarditis, meningoencephalitis
 No effective drug or vaccine is available
CMV Treatment
 Acyclovir is used for Hairy cell leukaemia
but not effective for Infectious  For neonates with symptomatic infection,
Mononucleosis treatment with ganciclovir may protect
against hearing loss and developmental
 Rituximab (antibody to CD20) is being used impairment
nowadays
 Roseola Infantum
 Also known as Sixth disease/exanthem  Small amounts of blood can transmit
infection
 an acute febrile disease in babies 2-12
months:  Sexually transmitted
 begins with fever, followed by a faint  High incidence among homosexuals & drug
maculopapular rash addicts
 usually self limited HBV and Disease
 RI is caused by HHV-6 & 7  Hepatitis: acute or chronic
 Adults may get mononucleosis like  30% -50% of adults develop significant
syndrome, hepatitis, lymphadenopathy, symptoms during acute infection
encephalitis & cancer
 The incubation period: 30-180 days
 HHV-8
• Symptoms of hepatitis include:
Kaposi sarcoma
 Fever, fatigue, dark urine, loss of appetite,
 Cancer of endothelial cells of blood vessels nausea, vomiting
 Commonly seen in HIV patients  Pain in the upper right abdomen- due to
inflamed liver
Primary effusion Lymphoma
 Chronic hepatitis may lead to: cirrhosis
Castleman’s Disease(Lymphoproliferative
or liver cancer
disease of B cells)
• Diagnosis
Hepadnaviruses
 serology of HBsAg or antibody response
 Infectious HBV virion (known as Dane
particle): • Treatment
 has partially ds DNA  No specific treatment for acute infection
 is 42 nm in diameter  chronic infection-controlled with interferon and reverse
and or tenofovir or entecavir transcriptase
 has icosahedral capsid inhibitors
 HB immune globulin protects exposed
 envelope containing HBsAg
people
• Hepatitis B virus (HBV) is the human
Prevention
pathogen in this family
 HBV vaccine – recombinant surface antigen
Hepatitis B virus
made by yeast; given in 3 doses over 18
 Has tropism for liver i.e. replicates months
exclusively in the liver
Human Papovaviruses
 Liver continuously seeds blood with viruses
• So called from original 3 agents grouped
(107 virions/ml)
in this family:
 HBV causes hepatitis & can be a factor in
 Papilloma
liver cancer
 Polyoma and
 Simian vacuolating agent (SV40)
• Now grouped into only two subfamilies: the  generally cause pain when walking
larger sized Papillomaviruses and smaller
 caused by HPV 1,2,4 and 63 strains
Polyomaviruses
 Flat warts
Human papillomavirus (HPV)
 found on the face, neck or areas that have
 HPV is a group of more than 150 related
been scratched
viruses
 generally affect children, adolescents and
 HPV is a virus which is transmitted through:
young adults
• skin-to-skin contact
 darker than normal skin colour
• through sexual intercourse or
 caused by HPV 3, 8 and 10 strains
• other forms of skin-to-skin contact of the
Genital warts
genitals
 usually appear as a small bump or groups of
• Some strains of HPV cause warts while
bumps in the genital area
others cause cancers
 they can be small or large, raised or flat, or
Incubation – 2 weeks – more than a year
shaped like a cauliflower
 HPV 6 and 11 strains account for about 90%
of all cases
 Strong association with cervical and penile
cancers
Diagnosis of HPV Infection
 Tests to evaluate for HPV or HPV-related
cervical cellular changes include:
• A Pap smear-to reveal abnormal cells in the
cervix Koilocytes present

Types of warts • DNA test-to evaluate for high-risk types of

HPV
Warts or papilloma (benign, squamous epithelial
growth) associated with HPV include: Treatment & Prevention

Common warts • Treatments:

 found on the hands and feet etc.  Warts may be removed with:

 are rough and raised  Podophyllin, Imiquimod, Podofilox,

Trichloroacetic acid
 caused by HPV 2, 7 and 22 strains
 freezing, laser surgery, immunotherapy
Plantar warts
• Prevention:
 found on the soles and heels of feet
• Abstinence
 are hard and grow inward
• monogamous sexual relationships
• not having sex with visible genital warts  type 3,4,7,14 & 21
• use of HPV vaccines (Gardasil, Cervarix)  Epidemic keratoconjunctivitis “shipyard
eye”, highly contagious, severe, but
Polyomavirus
usually no sequelae
Family: Polyomaviridae  type 8 & 19
• (formally grouped with papillomaviruses)
 Infantile diarrhea (gastroenteritis)-
• Closed, circular, ds DNA genome prevalent in third world and migrant
workers
• Non-enveloped, naked capsid
 type 40 & 41
• Icosahedral shape
Adenovirus Transmission
• Capsid: about 45 nm in diameter
 Spread exclusively human-to-human
Polyomaviruses John Cunningham virus
 Respiratory droplets
Poly=multiple & oma=tumour
 Iatrogenic transmission in eye disease
 May be shed intermittently and over long
periods from pharynx and faeces
Adenovirus Diagnosis & Prevention
 Diagnosis:
 Culture, electron microscopy (EM)
 Complement fixation test
 Treatment: none
 Prevention:
 Live vaccine against types 3,4, and 7 is used
Adenovirus Diseases in the military to prevent pneumonia
Medically important viruses: Parvoviruses
 Adenovirus
• There are two major subgroups:
 49 serotypes or 6 subgroups (A-F) • autonomous replicating
 Mild pediatric respiratory disease (prevalent • dependoviruses
0-6 yrs.)= type: 1,2 & 5
• Autonomous replicating- e.g. B19 which is
 Acute Respiratory Distress (ARD) (5-8% the only significant agent of human disease
adults & up to 50-80% of military recruits)
• Dependovirus-e.g. adeno-associated virus
 type 3,4,7,11,14 & 21 require a helper virus for replication
 Pharyngoconjunctival fever, eye Parvovirus Diseases
involvement as long as 3 weeks
• Erythema infectiosum or “fifth exanthem”, a Poxviruses
self-limited febrile illness of children with
• Largest and the most complex of all viruses
facial rash (“slapped cheek” syndrome)-
usually ages 4-15 years • Brick-like shape
• B19 is associated with “aplastic crises” in • Produce eruptive skin pustules called pocks
anemia and sickle-cell anaemia patients. It or pox, that leave scars
can also lead to idiopathic red cell aplasia in
AIDS patients • Two important members:

• In seronegative pregnant women it can cause • Variola: cause of smallpox

hydrops fetalis, where an aborted fetus is • Vaccinia: closely related virus used in the
delivered smallpox vaccine
• Less often: rheumatoid arthritis in young Smallpox
adults or hepatitis in children
• First disease to be eradicated (1980) through
• Slapped-cheek syndrome global immunization
Laboratory Diagnosis • Exposure through inhalation or direct
• Cannot readily be grown in the lab, contact with virus from lesions

• but can be found in the blood by EM during • Infection associated with fever, malaise,
the viremic stage prostration, & a rash

• Virus DNA can be identified by: • It is caused by either of the two variants:

• PCR • Variola major – highly virulent, cause

toxemia, shock, & intravascular
• Dot-blot hybridization coagulation
• For current or recent infection: • Variola minor –less virulent
• Detection of IgM antibody by ELISA • Diagnosis: EM, embryo culture
• Much more prolonged presence of IgG is a Reasons for Successful Eradication of
sign for past infection Smallpox
Control Methods  No animal reservoir
 No carriers
• No specific vaccine or antiviral therapy
 Subclinical cases do not transmit disease
• Prophylaxis with antibody is directed mainly  Case detection was easy
at prevention of spread to highly susceptible
Molluscum Contagiosum
people:
Molluscum contagiosum is caused by a virus
• Severe anaemia
(the molluscum contagiosum virus) that is part
• Lab staff who may be exposed to high of the pox virus family
concentration of virus
There are several ways it can spread:
• Immunoglobulins can be used to block
 Direct skin-to-skin contact
persistent infection with B19
 Indirect contact via shared towels or other Clinical Forms of Rubella
items
• Two clinical forms:
 Auto-inoculation into another site by
• Postnatal rubella – malaise, fever, sore
scratching or shaving
throat, lymphadenopathy, rash, generally
 Sexual transmission in adults mild, lasting about 3 days
 Presents as clusters of small round papules • Congenital rubella – infection during 1st
trimester most likely to induce
 The papules range in size from 1 to 6 mm
miscarriage or multiple defects such as
and may be white, pink or brown
cardiac abnormalities, ocular lesions,
 They often have a small central pit (this deafness, mental and physical
appearance is sometimes described as retardation
umbilicated)
• Diagnosis based on serological testing
• No specific treatment available
RNA VIRUSES OF MEDICAL
• Attenuated viral vaccine MMR
IMPORTANCE
Flaviviruses
Yellow fever virus
Dengue fever virus
West Nile virus
Zika virus
Hepatitis C virus
St Louis encephalitis
Japanese encephalitis etc.

*Icosahedral; the rest have helical symmetry Yellow Fever

Yellow fever (YF) virus found mainly in West
Africa and S America
Enveloped Positive Sense SS-RNA Viruses
Two patterns of transmission:
Togavirus-Rubivirus
 urban cycle – humans and mosquitoes,
• Causes Rubella (also known as German Aedes aegypti
measles)
 sylvan (jungle) cycle - forest monkeys and
• Rubella is transmitted through contact with mosquitoes
respiratory secretions
Acute fever, headache, muscle pain; may
• Endemic disease progress to oral hemorrhage, nosebleed,
• Most cases reported are among adolescents vomiting, jaundice, and liver and kidney
and young adults damage; significant mortality rate
Diagnosis: serology tests
Treatment & Prevention • Public education
Treatment • Vector control
 No specific treatments; hospitalization for • No Vaccine yet
supportive care and close observation
Zika
 Rest, fluids and use of pain relievers
It was discovered in the Zika forest in Uganda in
Prevention 1947
 Protection from mosquito bites The vast majority of infections are not
contagious from person to person
 Vaccination
Transmission
 Dakar vaccine: French Neurotropic vaccine
produced from infected mouse brain  through the bite of infected Aedes
mosquitoes (A. aegypti and A. albopictus)
 17D vaccine: Is an effective live attenuated
vaccine. It was developed by Theiler in 1937  vertical transmission from mother to child
by passaging the Asibi strain (African during pregnancy
patient) in mouse embryo
 Through sexual contact
Dengue Fever
Mostly asymptomatic. Fever rash, headache,
• Dengue fever – flavivirus (4 serotypes joint pain red eyes and muscle pain
(DEN1-4) carried by Aedes mosquito
• Zika virus infection during pregnancy can
• usually mild infection cause:
• dengue hemorrhagic shock syndrome, break- • microcephaly, a condition in which the
bone fever foetus has smaller head than normal
• extreme muscle and joint pain; can be fatal • other problems before birth, such as eye and
hearing defects and impaired growth
• Dengue haemorrhagic fever and shock
syndrome appear most often in patients • Rarely causes Guillain-Barre syndrome, a
previously infected by a different serotype serious condition of the nervous system
of dengue, thus suggesting an
immunopathological mechanism • Diagnosis: serology, PCR

• Dengue is found on SE Asia, Africa, the

Caribbean and S America Treatment & Prevention
• Diagnosis: serology, PCR, virus isolation, Treatment
PRNT= Plaque Reduction and
Neutralization  No commercial vaccine or specific antiviral
drug treatment for Zika virus infection
Treatment & Prevention
 Treatment is directed primarily at relieving
Treatment symptoms using anti-pyretics and analgesics
medicine
• No specific therapy, only supportive care
Prevention
Prevention
 Public education • Treatment with interferon and ribavirin to
lessen liver damage; no cure
 Vector control
• No vaccine
West Nile Fever
Retroviruses
• West Nile Virus (WNV) was first isolated in
a woman in the West Nile district of Uganda • Two genera of human interest:
in 1937
• Lentivirus (Lentus=slow)
• Transmission
 Human immunodeficiency virus 1 & 2 (HIV-1
• WNV commonly spreads to people by & -2)-first emerged early 1980s
mosquito bites. Birds are the natural hosts
• Asymptomatic in 80% of cases
 Oncovirus group
• The symptoms of severe disease (also called
 Human T- cell lymphotropic virus-bovine
neuroinvasive disease, such as West Nile
leukemia virus group)
encephalitis or meningitis) include:
 Human T-cell leukemia viruses 1, 2 & 5
• headache, high fever, neck stiffness, stupor,
(HTLV-1, -2 & -5)
disorientation, coma, tremors, convulsions,
muscle weakness and paralysis HIV & AIDS
Diagnosis & Treatment • HIV encodes reverse transcriptase enzyme
which makes a double stranded DNA from
• Diagnosis: ELISA for IgM antibodies, PCR
the single-stranded RNA genome
• Treatment
• Viral genes permanently integrated into host
• Supportive often involving hospitalization, DNA
intravenous fluids, respiratory support and
• HIV the cause of Acquired
prevention of secondary infections
Immunodeficiency Syndrome (AIDS)
• No vaccine is available for humans
• The virus requires two receptors to enter
Hepatitis C Virus (HCV) cells:
• Non-A non-B virus • CD4 receptor
• Acquired through blood contact – blood • chemokine receptors (CCR5 & CXCR4)
transfusions, needle sharing by drug abusers
Pathogenesis and Virulence Factors of HIV
• Infections with varying characteristics -75-
• HIV enters through mucous membrane or
85% will remain infected indefinitely;
skin and travels to dendritic phagocytes
possible to have severe symptoms without
beneath the epithelium, multiplies and is
permanent liver damage; more common to
shed
have chronic liver disease, without overt
symptoms • Virus is taken up and amplified by
macrophages in the skin, lymph organs,
• Cancer may also result from chronic HCV
bone marrow, and blood
infection
• HIV attaches to CD4 and coreceptor; HIV • They experience one or more of a CDC-
fuses with cell membrane provided list of AIDS-defining illnesses
• Reverse transcriptase makes a DNA copy of Preventing and Treating HIV
RNA
• No vaccine available
• Viral DNA is integrated into host
• monogamous sexual relationships
chromosome (provirus)
• condoms
• Can produce a lytic infection or remain
latent • universal precautions
Stages in HIV infection • No cure; therapies slow down the progress
of the disease or diminish the symptoms
3 phases:
 acute, • inhibit viral enzymes: reverse transcriptase,
protease, integrase
 latent (asymptomatic)
• inhibit fusion
 symptomatic/advanced HIV disease (AIDS)
• inhibit viral translation
Diagnosis of HIV Infection
• highly active anti-retroviral therapy
• Testing based on detection of antibodies
specific to the virus in serum or other fluids; Coronaviruses
done at 2 levels: • Relatively large RNA viruses with
• Initial screening distinctively spaced spikes on their
envelopes
• ELISA, latex agglutination and rapid
antibody tests • Common in domesticated animals
• 3 types of human coronaviruses have been
• rapid results but may result in false positives
characterized:
• Follow up with Western blot analysis to rule
out false positives • HCV causes a cold

• can also occur; persons who may have been • an enteric virus
exposed should be tested a second time 3-6 • Severe Acute Respiratory Syndrome
months later (SARS)
Diagnosis of AIDS is made when a person • airborne transmission
meets the criteria:
• 10% of cases fatal
• Positive for the virus, and
Severe Acute Respiratory Syndrome-
• They fulfill one of the additional criteria: Associated Coronavirus (SARS)
• They have a CD4 count of fewer than 200 • Newly emerging disease – 2002
cells/ml of blood
• Transmitted through droplet or direct contact
• Their CD4 cells account fewer than14% of
all lymphocytes • Fever, body aches, and malaise
• May or may not experience respiratory • Invasion of motor neurons causes flaccid
symptoms with breathing problems; severe paralysis
cases can result in respiratory distress and
• Decades later post-polio syndrome (PPS) –
death
progressive muscle deterioration; occurs in
• Diagnosis relies on exclusion of other likely 25-50% of patients infected with
agents polioviruses in childhood
• Treatment is supportive Treatment and Prevention
• Treatment is largely supportive for pain and
suffering; respiratory failure may require
Nonenveloped Positive Sense SS-RNA Viruses
artificial ventilation; physical therapy may
Picornaviruses be needed

• Enterovirus – poliovirus • Prevention is vaccination

• Rhinovirus – rhinovirus • Inactivated polio vaccine (IPV)-Salk vaccine

Poliovirus and Poliomyelitis • Oral polio vaccine (OPV) (attenuated)-Sabin

vaccine
• Poliomyelitis (polio) – acute enteroviral
infection of the spinal cord that can cause Nonpolio Enteroviruses
neuromuscular paralysis
• Coxsackieviruses A and B
• Poliovirus – naked capsid; resistant to acid,
• Echoviruses
bile, and detergents; can survive stomach
acids when ingested • Similar to poliovirus in epidemiological and
infectious characteristics but less virulent
• Worldwide vaccination programs have
reduced the number of cases; eradication is • Responsible for respiratory infections,
expected conjunctivitis, and hand-foot-mouth disease
• Transmitted by fecal-oral route • Rare cases of coxsackievirus and echovirus
paralysis, aseptic meningitis, and
• Polioviruses adhere to receptors of mucosal
encephalitis
cells in oropharynx and intestine, multiply
in number and shed in throat and feces, Hepatitis A Virus
some leak into blood
• Cubical picornavirus relatively resistant to
• Most infections are short-term, mild viremia heat and acid
• Some develop mild nonspecific symptoms • Not carried chronically, principal reservoirs
of fever, headache, nausea, sore throat, and are asymptomatic, short-term carriers or
myalgia people with clinical disease
• If viremia persists, virus spreads to spinal • Fecal-oral transmission; multiplies in small
cord and brain intestine and enters the blood and is carried
to the liver
• If nervous tissue is infected but not
destroyed – muscle pain and spasm, • Most infections subclinical or vague, flu-like
meningeal inflammation symptoms occur; jaundice is seldom present
• No specific treatment once the symptoms • Virus attaches to, and multiplies in, the cells
begin of the respiratory tract; finished viruses are
assembled and budded off
• Inactivated viral vaccine
• Influenza virus has glycoprotein spikes:
• Attenuated viral vaccine
• hemagglutinin (H) – 15 different subtypes;
• Pooled immune serum globulin for those
most important virulence factor; binds to
entering into endemic areas
host cells
Human Rhinovirus (HRV) • neuraminidase (N) – 9 subtypes –
• More than 110 serotypes associated with the hydrolyzes mucus and assists viral budding
common cold and release

• Headache, chills, fatigue, sore throat, cough, • Both glycoproteins frequently undergo
nasal drainage genetic changes decreasing the effectiveness
of the host immune response
• Sensitive to acidic environments; optimum
temperature is 33oC • Constant mutation is called, antigenic drift -
gradually change their amino acid
• Endemic with many strains circulating in the composition
population at one time; acquired from
contaminated hands and fomites • Antigenic shift – one of the genes or RNA
strands is substituted with a gene or strand
• Treat the symptoms from another influenza virus from a different
• Handwashing and care in handling nasal animal host
secretions
Caliciviruses
• Norwalk agent (Norovirus) best known;
believed to cause 1/3rd of all viral
gastroenteritis (cruise ships)
• Transmitted by fecal-oral route
• Infection in all ages at any time of year
• Acute onset, nausea, vomiting, cramps,
diarrhea, chills Influenza B & C

• Rapid and complete recovery • Influenza B

Enveloped Negative Sense SS-RNA Viruses • Not known to undergo antigenic shift

Orthomyxoviruses: Influenza • Influenza C

• consists of 10 genes encoded on 8 separate • Known to cause only minor respiratory

RNA segments disease; probably not involved in epidemics

• 3 distinct influenza virus types: A, B, C; Diagnosis, Treatment & Prevention

• Type A causes most infections Diagnosis

• Rapid immunofluorescence tests to detect • Incubation 2-3 weeks fever, muscle pain and
antigens in a pharyngeal specimen; malaise, classic swelling of one or both
serological testing to screen for antibody cheeks
titer
• Usually uncomplicated invasion of other
Treatment organs; in 20-30% of infected adult males,
epididymis and testes become infected;
 Control symptoms; amantadine,
sterility is rare
rimantadine, zanamivir (Relenza) and
oseltamivir (Tamiflu) • Live attenuated vaccine MMR
 Flu virus has developed high rate of Measles
resistance to amantadine and rimantadine
• Caused by Morbillivirus
Prevention
• Also known as red measles and rubeola
 Annual trivalent vaccine recommended
• Different from German measles
Paramyxoviruses
• Very contagious; transmitted by respiratory
• Parainfluenza, mumps virus, measles virus, aerosols
respiratory syncytia virus
• Humans are the only reservoir.
• Respiratory transmission
• Sore throat, dry cough, headache,
• Envelope has HN and specialized F spikes conjunctivitis, lymphadenitis, fever, Koplik
that initiate cell-to-cell fusion spots – oral lesions
• Fusion with neighboring cells – syncytium • Exanthem
or multinucleate giant cells form
• Most serious complication is subacute
Parainfluenza sclerosing panencephalitis (SSPE), a
progressive neurological degeneration of the
• Widespread as influenza but more benign
cerebral cortex, white matter and brain stem
• Respiratory transmission
• 1 case in a million infections
• Seen mostly in children
• Involves a defective virus spreading through
• Minor cold, bronchitis, bronchopneumonia, the brain by cell fusion and destroys cells
croup
• Leads to coma and death in months or years
• No specific treatment available; supportive
• Attenuated viral vaccine MMR
therapy
Respiratory Syncytial Virus (RSV)
Mumps
• Also called Pneumovirus
• Epidemic parotitis; self-limited, associated
with painful swelling of parotid salivary • Infects upper respiratory tract and produces
glands giant multinucleate cells
• Humans are the only reservoir • Most prevalent cause of respiratory infection
in children 6 months or younger; most
• 40% of infections are subclinical; long-term
susceptible to serious disease
immunity
• Epithelia of nose and eye portal of entry; • Bite from wild or stray animals demands
replicates in nasopharynx assessment of the animal, meticulous wound
care, and specific treatment
• Fever, rhinitis, wheezing, otitis, croup
• Preventive therapy initiated if signs of rabies
• Treatment: synagis, a monoclonal antibody
appear
that blocks attachment, ribavirin
• Treatment – passive and active postexposure
Rhabdovirus-Rabies immunization
• bullet-shaped virion
• infuse the wound with human rabies
• Slow, progressive zoonotic disease immune globulin (HRIG) and globulin;
vaccination with human diploid cell vaccine
• Primary reservoirs are wild mammals; it can (HDCV), an inactivated vaccine given in 6
be spread by both wild and domestic doses with 2 boosters
mammals by bites, scratches, and inhalation
of droplets • Control: vaccination of domestic animals,
elimination of strays, and strict quarantine
practices
• live oral vaccine incorporated into bait for
wild animals
Arenaviruses
Transmitted zoonotically; cause periodic
epidemics; extremely dangerous; biosafety level
4 viruses
Lassa fever and Lymphocytic choriomeningitis
 Closely associated with rodent host
 Transmission through aerosols and contact
Filoviruses
Clinical Phases of Rabies
• Marburg virus
• Prodromal phase: fever, nausea, vomiting,
headache, fatigue; some experience pain, • Ebola virus-Five species have been
burning, tingling sensations at site of wound identified:

• Furious phase: agitation, disorientation, • Taï Forest (formerly Ivory Coast)

seizures, twitching, hydrophobia
• Sudan
• Dumb phase: paralyzed, disoriented,
• Zaire
stuporous
• Reston (does not cause severe disease in
• Progress to coma phase, resulting in death
humans)
Treatment & Prevention
• Bundibugyo
• Often diagnosed at autopsy – intracellular
Ebola Virus Disease
inclusions (Negri bodies) in nervous tissue
Ebola, which first appeared in Sudan and DR • treatment with rehydration and electrolyte
Congo in 1976 is a severe and often fatal disease replacement
with no known treatment or vaccine
• Reovirus – cold-like upper respiratory
Source infection, enteritis
Africa, particular species of fruit bats are
considered possible natural hosts for Ebola virus
Transmission
Infected bats are thought to transmit the disease
to humans or indirectly through other animals
which are hunted for their meat
Damage
Incubation period is from 2-21days. Death from
the disease is often caused by multiple organ
failure

Nonenveloped dsRNA Viruses

Reoviruses
• Unusual double-stranded RNA genome
• Two best known:
• Rotavirus – oral-fecal transmission; primary
viral cause of mortality and morbidity
resulting from diarrhea in infants and
children