Viruses and Viral Diseases

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Viruses and Viral Diseases
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General Structure of Viruses

• Size range
• most lt0.2 µm
• requires electron microscope
• Virion
• fully formed virus able to establish an infection

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General Structure of Viruses

• Capsids
• All viruses have capsids
• Constructed from identical subunits called
  capsomers
• made of protein
• nucleoscapsid
• Capsid nucleic acid
• Enveloped
• Naked

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General Structure of Viruses

• Two structural types
• helical
• Continuous helix of capsomers forming a
  cylindrical nucleocapsid
• icosahedral
• 20-sided with 12 corners
• vary in the number of capsomers
• Each capsomer may be made of 1 or several
  proteins
• Some are enveloped

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Icosahedral
Helical
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General Structure of Viruses

• Viral envelope
• mostly animal viruses
• acquired when the virus leaves the host cell
• spikes
• exposed proteins on the outside of the envelope
• essential for attachment of the virus to the host
  cell

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General Structure of Viruses

• Functions of Capsid/Envelope
• Protects the nucleic acid when the virion is
  outside the host cell
• Helps to bind the virion to a cell surface
• assists the penetration of the viral DNA or RNA
  into a suitable host cell

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Viral morphology (a) poxvirus, (b)
bacteriophage, (c) mumps, (d) herpesvirus, (e)
rhabdovirus, (f) HIV, (g) adenovirus, and (h)
papillomavirus.
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General Structure of Viruses

• Complex viruses atypical viruses
• Poxviruses
• lack a typical capsid
• covered by a dense layer of lipoproteins
• Bacteriophages
• Some have a polyhedral nucleocapsid along with a
  helical tail and attachment fibers

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Nucleic acids

• Viral genome
• either DNA or RNA but never both
• Carries genes necessary to invade host cell
• then redirect cells activity to make new viruses
• Number of genes varies for each type of virus
• few to hundreds

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Nucleic Acids

• DNA viruses
• usually double stranded (ds)
• may be single stranded (ss)
• circular or linear

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Nucleic Acids

• RNA viruses
• usually single stranded
• may be double stranded
• may be segmented into separate RNA pieces
• positive-sense RNA
• ssRNA genomes ready for immediate translation
• negative-sense RNA
• ssRNA genomes that must be converted into proper
  form

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Naming Viruses

• 3 Orders
• Order name end in virales
• Herpesvirales
• 63 Families
• Family name ends in -viridae
• Herpesviridae
• 263 genera
• Genus name ends in virus
• Simplexvirus, Herpes simplex virus I (HSV-I)

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Naming Viruses

• Family Herpesviridae
• Genus Varicellovirus
• Common name chickenpox virus
• Disease - chickenpox

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Modes of Viral Multiplication
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6 Steps in Viral Replication

• adsorption
• penetration
• replication
• assembly
• maturation
• release

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1. Adsorption and Host Range

• Virus coincidentally collides with a susceptible
  host cell
• adsorbs specifically to receptor sites on the
  cell membrane
• Attachment
• host range
• Spectrum of cells a virus can infect
• hepatitis B human liver cells
• poliovirus primate intestinal and nerve cells
• Rabies various cells of many mammals

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2. Penetration/Uncoating

• Flexible cell membrane penetrated by the whole
  virus (or its nucleic acid) by
• endocytosis
• entire virus engulfed and enclosed in a vacuole
  or vesicle
• fusion
• envelope merges directly with membrane
• Results in nucleocapsids entry into cytoplasm

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3. Replication

• Varies depending on whether the virus is a DNA or
  RNA virus
• DNA viruses generally are replicated and
  assembled in the nucleus
• RNA viruses generally are replicated and
  assembled in the cytoplasm

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4. 5. Assembly and Maturation

• Mature viruses made from various parts
• Capsid laid down first
• Enveloped
• Insert viral spikes

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6. Release

• Assembled viruses leave host cell in one of two
  ways
• budding
• exocytosis
• nucleocapsid binds to membrane which pinches off
  and sheds the viruses gradually
• cell is not immediately destroyed
• lysis
• nonenveloped and complex viruses released when
  cell dies and ruptures
• Number of virions released is variable
• 3,000-4,000 released by poxvirus
• gt100,000 released by poliovirus

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Damage to Host Cell

• Cytopathic effects - virus-induced damage to
  cells
• Changes in size shape
• Cytoplasmic inclusion bodies
• Nuclear inclusion bodies
• Cells fuse to form multinucleated cells
• Cell lysis
• Alter DNA
• Transform cells into cancerous cells

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Persistent Infections

• Persistent infections
• cell harbors the virus and is not immediately
  lysed
• chronic / latent state
• Can last weeks or hosts lifetime
• several can periodically reactivate
• measles virus
• may remain hidden in brain cells for many years
• herpes simplex virus
• cold sores and genital herpes
• herpes zoster virus
• chickenpox and shingles

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Transformation

• transformation of the cell
• Some animal viruses enter host cell and
  permanently alter its genetic material
• resulting in cancer
• Transformed cells have increased rate of growth,
  alterations in chromosomes, and capacity to
  divide for indefinite time periods
• resulting in tumors
• oncoviruses
• Mammalian viruses capable of initiating tumors
• Papillomavirus cervical cancer
• Epstein-Barr virus Burkitts lymphoma

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Multiplication Cycle in Bacteriophages

• Bacteriophages bacterial viruses (phages)
• Most widely studied are those that infect
  Escherichia coli
• Multiplication goes through similar stages as
  animal viruses
• Only the nucleic acid enters the cytoplasm
• uncoating not necessary
• Release is a result of cell lysis induced by
  viral enzymes and accumulation of viruses
• Lytic cycle

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Lysogeny

• Not all bacteriophages lyse cells
• Temperate phages
• insert their viral DNA into host chromosome
• viral replication stops there until some later
  time
• Lysogeny
• bacterial chromosome carries phage DNA

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Lysogeny

• Results in the spread of the virus without
  killing the host cell
• lysogenic conversion
• Phage genes in the bacterial chromosome cause the
  production of toxins or enzymes that cause
  pathology
• Corynebacterium diphtheriae
• Vibrio cholerae
• Clostridium botulinum

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Techniques in Cultivating and Identifying Animal
Viruses

• Obligate intracellular parasites require
  appropriate cells to replicate
• In vitro
• In vivo
• Methods used
• cell (tissue) cultures
• bird embryos
• live animal inoculation

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Techniques in Cultivating and Identifying Animal
Viruses

• Cell (tissue) cultures
• cultured cells grow in sheets that support viral
  replication
• permit observation for cytopathic effect

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Techniques in Cultivating and Identifying Animal
Viruses

• Bird embryos
• incubating egg is an ideal system
• virus is injected through the shell

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Techniques in Cultivating and Identifying Animal
Viruses

• live animal inoculation
• occasionally used when necessary

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Other noncellular infectious agents

• Satellite viruses
• dependent on other viruses for replication
• adeno-associated virus
• replicate only in cells infected with adenovirus
• delta agent
• naked strand of RNA expressed only in the
  presence of hepatitis B virus
• Viroids
• short pieces of RNA
• no protein coat
• only identified in plants so far

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DNA viruses that infect humans
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Viruses

• Most DNA viruses are budded off the nucleus
• Most RNA viruses multiply in are released from
  the cytoplasm
• Viral infections range from very mild to
  life-threatening
• Many viruses are strictly human in origin, others
  are zoonoses transmitted by vectors
• Most DNA a few RNA viruses can become permanent
  resident of the host cell
• Several viruses can cross the placenta cause
  developmental disturbances

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Survey of DNA Viruses

• Animal viruses are categorized according to
• nucleic acid
• Capsid
• presence / absence of envelope
• 7 DNA families, 14 RNA families
• DNA viruses causing human disease
• enveloped DNA viruses
• nonenveloped DNA viruses
• nonenveloped ssDNA viruses

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Enveloped DNA Viruses
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1. Poxviruses

• Produce eruptive skin pustules called pocks or
  pox
• Largest and most complex animal viruses
• Have the largest genome of all viruses
• dsDNA
• Multiply in cytoplasm in factory areas
• variola cause of smallpox
• vaccinia closely related virus used in vaccines
• monkeypox
• cowpox

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Smallpox

• first disease to be eliminated by vaccination
• exposure through inhalation or skin contact
• infection associated with fever,
• malaise, prostration, a rash
• Variola major
• highly virulent, caused toxemia, shock,
  intravascular coagulation
• Variola minor
• less virulent
• routine vaccination ended in US in 1972
• reintroduced in 2002

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Molluscum Contagiosum

• caused by unclassified poxvirus
• in endemic areas it is primarily an infection of
  children
• in US, most commonly an STD
• transmitted by direct contact and
• fomites
• AIDS patients suffer atypical form
• attacks the skin of the face
• forms tumorlike growths
• Treatment
• freezing, electric cautery, chemical agents

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Other Poxviruses

• Many mammalian groups host some poxvirus
• Humans are susceptible to monkeypox and cowpox
• Monkeypox in humans
• skin pocks, fever, swollen lymph nodes
• Cowpox in humans
• rare, usually confined to hands
• other cutaneous sites can be involved

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2. The Herpesviruses

• All members show latency and cause recurrent
  infection
• more severe with advancing age, cancer
  chemotherapy, or other conditions that compromise
  the immune defenses
• Common and serious opportunists among AIDS
  patients
• Large enveloped icosahedral dsDNA
• Replicates within nucleus

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Herpesviridae

• large Family 8 infect humans
• HSV-1
• HSV-2
• VZV
• CMV
• EBV
• HHV-6
• HHV-7
• HHV-8

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Herpes Simplex Viruses

• HSV-1
• lesions on the oropharynx, cold sores, fever
  blisters
• occurs in early childhood
• HSV-2
• lesions on the genitalia
• occurs in ages 14-29
• can be spread without visible lesions
• Humans only reservoir
• Treatment
• acyclovir, famciclovir, valacyclovir

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Epidemiology

• Transmission
• direct exposure to secretions containing the
  virus
• active lesions most significant source
• genital herpes can be transmitted in the absence
  of lesions
• HSV multiplies in sensory neurons, moves to
  ganglia
• HSV-1 enters 5th cranial nerve
• HSV-2 enters lumbosacral spinal nerve trunk
  ganglia

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Epidemiology

• Recurrent infection triggered by various stimuli
• fever, UV radiation, stress, mechanical injury
• Newly formed viruses migrate to body surface
• produce a local skin or membrane lesion

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Type 1 Herpes Simplex

• Herpes labialis
• fever blisters, cold sores
• most common recurrent HSV-1 infection
• vesicles occur on mucocutaneous junction of lips
  or adjacent skin
• itching and tingling prior to vesicle formation
• lesion crusts over in 2-3 days and heals
• Herpetic gingivostomatitis
• infection of oropharynx in young children
• fever, sore throat, swollen lymph nodes
• Herpetic keratitis
• ocular herpes

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Type 2 Herpes Infections

• Genital herpes
• herpes genitalia
• starts with malaise, anorexia, fever, and
  bilateral swelling and tenderness in the groin
• clusters of sensitive vesicles on the genitalia,
  perineum, and buttocks
• urethritis, painful urination
• Recurrent bouts usually less severe
• triggered by menstruation, stress, and concurrent
  bacterial infection

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Herpes of the Newborn

• HSV-1 and HSV-2
• Potentially fatal in the neonate and fetus
• Infant contaminated by mother before or during
  birth
• hand transmission by mother to infant
• Infection of mouth, skin, eyes, CNS
• Preventative screening of pregnant women
• delivery by C-section if outbreak at the time of
  birth

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Diagnosis, Treatment, and Control

• Vesicles and exudate are typical diagnostic
  symptoms
• scrapings from base of lesions showing giant
  cells
• culture and specific tests for diagnosing severe
  or disseminated HSV
• direct fluorescent antibody tests
• Treatment
• acyclovir, famciclovir, valacyclovir topical
  medications

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Varicella-Zoster Virus (VZV)

• HSV-3
• chickenpox shingles
• transmitted by respiratory droplets contact
• primary infection
• Chickenpox
• vesicles

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Varicella-Zoster Virus (VZV)

• virus enters neurons remains latent
• later reactivation of the virus results in
  shingles with vesicles localized to distinctive
  areas
• dermatomes
• treatment
• acyclovir, famciclovir, interferon
• live attenuated vaccine
• Contagiousness and spread

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Cytomegalovirus (CMV)

• HSV-4
• produce giant cells with nuclear cytoplasmic
  inclusions
• transmitted in saliva, respiratory mucus, milk,
  urine, semen, cervical secretions feces
• commonly latent in various tissues
• most infections are asymptomatic
• 3 groups develop a more virulent form of disease
• fetuses, newborns, immunodeficient adults

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CMV

• newborns may exhibit enlarged liver spleen,
  jaundice, capillary bleeding microcephaly,
  ocular inflammation, may be fatal
• perinatal CMV infection
• mostly asymptomatic, or pneumonitis, and a
  mononucleosis-like syndrome
• transplant patients
• pneumonitis, hepatitis, myocarditis,
  meningoencephalitis
• Treatment
• ganciclovir, valvcyclovir, foscarnet

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Epstein-Barr Virus (EBV)

• HSV-5
• infects lymphoid tissue salivary glands
• transmission
• direct oral contact contamination with saliva
• by mid-life 90-95 of all people are infected
• causes mononucleosis
• sore throat, high fever, cervical lymphadenopathy

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Epstein-Barr Virus (EBV)

• 30-50 day incubation
• most cases asymptomatic
• Burkitts lymphoma associated with chronic
  co-infections with malaria
• nasopharyngeal carcinoma in Chinese African men

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Diagnosis, Treatment and Prevention

• Differential blood count
• serological assays to detect antibodies and
  antigen
• Treatment directed at relief of symptoms of fever
  and sore throat
• Disseminated disease may be treated with IV gamma
  globulin, interferon, acyclovir, and monoclonal
  antibodies

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Human Herpes Virus 6

• HHV-6
• T-lymphotropic virus
• transmitted by close contact
• very common
• causes roseola
• an acute febrile disease in babies 2-12 months
• can cause encephalitis, cancer

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Human Herpes Virus 6

• begins with fever, followed by a faint
  maculopapular rash
• usually self-limited
• adults may get mono-like symptoms,
  lymphadenopathy, hepatitis
• over 70 of MS patients show signs of infection

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Human Herpes Virus 7 8

• HHV-7 is closely related to HHV-6 causes similar
  diseases
• Kaposis sarcoma
• associated virus or HHV-8 is linked with common
  tumor of AIDS patients
• also may be involved in multiple myeloma

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3. The Viral Agents of Hepatitis

• Hepatitis
• an inflammatory disease of liver cells
• may result from several viruses
• Interferes with livers excretion of bile
  pigments
• bilirubin accumulates in blood and tissues
  causing jaundice
• 3 principal viruses involved in hepatitis
• hepatitis B
• hepatitis A (RNA virus)
• hepatitis C (RNA virus)

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Hepadnaviruses

• enveloped DNA viruses
• never grown in tissue culture
• unusual genome containing both double single
  stranded DNA
• tropism for liver
• Hepatitis B virus causes hepatitis can be a
  factor in liver cancer
• other members cause hepatitis in woodchucks,
  ground squirrels, Peking ducks

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Hepatitis B Virus

• multiplies exclusively in the liver
• continuously seeds blood with viruses
• 107 virions/mL blood
• minute amounts of blood can transmit infection
• sexually transmitted
• high incidence among homosexuals drug addicts
• can become a chronic infection
• increases risk of liver cancer

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Pathogenesis of Hepatitis B Virus

• Enters through break in skin or mucous membrane
  or by injection into bloodstream
• Reaches liver cells
• multiplies and releases viruses into blood
• average 7 week incubation
• Most exhibit few overt symptoms and eventually
  develop HBV immunity
• Some experience malaise, fever, chills, anorexia,
  abdominal discomfort and diarrhea
• Fever, jaundice, rash, and arthritis are common
• Small number of patients develop chronic liver
  disease
• necrosis and cirrhosis

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Diagnosis and Management of Hepatitis B

• Diagnosis based on
• examination of risk factors
• serological tests to detect viral antibodies or
  antigen
• radioimmunoassay and ELISA tests for surface
  antigens
• Screening of blood for transfusion, semen for
  sperm banks, organs for transplant, and routine
  prenatal testing of all pregnant women
• Mild cases managed by treatment of symptoms and
  supportive care
• chronic infections treated with interferon

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Nonenveloped DNA Viruses
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1. Adenoviruses

• nonenveloped, ds DNA
• 30 types associated with human disease
• infect lymphoid tissue, respiratory intestinal
  epithelia conjunctiva
• oncogenic in animals, not in humans
• spread by respiratory ocular secretions
• causes colds, pharyngitis, conjunctivitis,
  keratoconjunctivitis, acute hemorrhagic cystitis
• inactivated polyvalent vaccine

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2. Papillomavirus

• papilloma
• benign, squamous epithelial growth, wart or
  verruca
• caused by 100 different strains of HPV
• common seed warts
• Fingers
• plantar warts
• soles of feet
• genital warts
• prevalent STD
• transmissible through direct contact or
  contaminated fomites
• Incubation
• 2 weeks more than a year

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Genital Warts

• most common STD in US
• over 6 M new cases each year
• 30 M carriers of one of the 5 types of HPV
  associated with genital warts
• strong association with cervical penile cancer
• type 16 18
• Treatment
• podophyllin chemical treatment, cauterization,
  freezing, laser surgery, immunotherapy

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3. Polyomaviruses

• induce tumors
• JC BK viruses
• common throughout the world
• majority of infections are asymptomatic or mild
• BK infection in renal transplants causes
  complications in urinary function

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4. Parvoviruses

• nonenveloped icosahedral, ssDNA
• small diameter genome size
• causes distemper in cats, enteric disease in
  dogs, fatal cardiac infection in puppies
• B19
• cause of fifth disease, erythema infectiosum rash
  of childhood
• Child may have fever rash on cheeks
• Severe fatal anemia can result if pregnant woman
  transmits virus to fetus

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RNA viruses
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RNA Viruses

• Assigned to one of 12 families based on envelope,
  capsid, and nature of RNA genome

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Enveloped Segmented Single-Stranded RNA Viruses
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1. Orthomyxoviruses

• Influenza
• ssRNA
• consists of 10 genes encoded on 8 separate RNA
  segments
• 3 distinct influenza virus types A, B, C
• Virus attaches to, and multiplies in, the cells
  of the respiratory tract
• finished viruses are assembled and budded off

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Insert figure 25.1 Influenza cycle
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Influenza Type A

• acute, highly contagious respiratory illness
• respiratory transmission
• causes rapid shedding of cells, stripping the
  respiratory epithelium, severe inflammation
• fever, headache, myalgia, pharyngeal pain,
  shortness of breath, coughing
• Treatment
• amantadine, rimantadine, zanamivir oseltamivir
• annual trivalent vaccine

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2. Bunyavruses Arenaviruses

• enveloped, segmented ssRNA
• transmitted zoonotically
• cause periodic epidemics
• Lassa fever, Argentine hemorrhagic fever,
  Bolivian hemorrhagic fever, Lymphocytic
  chroiomeningitis
• closely associated with rodent host
• transmission through aerosols contact
• biosafety level 4 viruses

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Enveloped Nonsegmented ssRNA Viruses
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1. Paramyxoviruses

• enveloped ssRNA
• Paramyxoviruses (parainfluenza, mumps virus)
• Morbillivirus (measles virus)
• Pnuemonovirus (respiratory syncytia virus)
• respiratory transmission
• virus causes infected cells to fuse with
  neighboring cells
• syncytium or multinucleated giant cells form

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Parainfluenza

• Paramyxoviruses
• widespread as influenza
• more benign
• respiratory transmission
• seen mostly in children
• minor cold, bronchitis, bronchopneumonia, croup
• no specific treatment available

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Mumps

• Paramyxoviruses
• epidemic parotitis
• self-limited, associated with painful swelling of
  parotid salivary glands
• humans are the only reservoir
• incubation 2-3 weeks fever, muscle pain
  malaise, classic swelling of both cheeks
• in 20-30 of infected males, epididymis testes
  become infected
• sterilization is rare
• live attenuated vaccine MMR

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Measles

• Morbillivirus
• also known as red measles rubeola
• very contagious
• transmitted by respiratory aerosols
• humans are the only reservoir
• sore throat, dry cough, headache, conjunctivitis,
  lymphadenitis, fever, Koplik spots
• oral lesions
• Rash

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Measles

• most serious complication is subacute sclerosing
  panencephalitis (SSPE)
• progressive neurological degeneration of the
  cerebral cortex, white matter brain stem
• 1 case in a million infections
• involves a defective virus spreading through the
  brain by cell fusion destroys cells
• leads to coma death in months or years
• attenuated viral vaccine MMR

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RSV

• also called Pneumonvirus
• infects upper respiratory tract produces giant
  multinucleate cells
• most prevalent cause of respiratory infection in
  children 6 months or younger
• epithelia of nose eye portal of entry
• replicates in nasopharynx
• rhinitis, wheezing, otitis, croup
• Treatment
• synagis, a monoclonal antibody that blocks
  attachment, ribavirin

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2. Rabies

• Rhabdovirus family
• bullet-shaped virions
• enveloped
• slow, progressive zoonotic disease

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Rabies

• virus enters through bite, grows at trauma site
  for a week
• enters nerve endings advances toward the
  ganglia, spinal cord brain
• furious form of rabies
• agitation, disorientation, seizures, twitching,
  hydrophobia
• dumb form of rabies
• paralyzed, stuporous

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Rabies

• often diagnosed at autopsy
• intracellular inclusions (Negri bodies) in
  nervous tissue
• treatment
• passive active postexposure immunization
• Days 1, 3, 7, 14, 28, 60

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Other enveloped RNA viruses
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1. Coronavirus

• large RNA viruses
• distinctively spaced spikes on their envelopes
• common in domesticated animals
• 3 types of human coronaviruses have been
  characterized
• HCV causes a cold
• an enteric virus
• Severe Acute Respiratory Syndrome (SARS)
• airborne transmission
• 10 of cases fatal

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SARS

• Severe Acute Respiratory Syndrome-Associated
  Coronavirus
• Newly emerging disease 2002
• Transmitted through droplet or direct contact
• Fever, body aches, and malaise
• severe cases can result in respiratory distress
  and death
• Diagnosis relies on exclusion of other likely
  agents
• Treatment is supportive

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2. Rubella

• Caused by Rubivirus, a Togavirus
• ssRNA with a loose envelope
• German measles
• Endemic disease
• Most cases reported are adolescents and young
  adults
• Transmitted through contact with respiratory
  secretions

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Rubella

• Two clinical forms
• Postnatal rubella
• generally mild
• malaise, fever, sore throat, lymphadenopathy,
  rash
• lasting about 3 days
• Congenital rubella
• infection during 1st trimester most likely to
  induce miscarriage or multiple defects
• Diagnosis based on serological testing
• No specific treatment available
• Attenuated viral vaccine MMR

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Arboviruses
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Arboviruses

• viruses that spread by arthropod vectors
• mosquitoes, ticks, flies, gnats
• 400 viruses
• togaviruses, flaviviruses, some bunyaviruses
  reoviruses
• most illnesses caused by these viruses are mild
  fevers, some cause severe encephalitis
• dengue fever, western- eastern equine
  encephalitis, yellow fever

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The Influence of the Vector

• Vectors and viruses tend to be clustered in the
  tropics and subtropics
• many temperate zones have periodic epidemics
• life cycles are closely tied to the ecology of
  the vectors
• peak incidence when the arthropod is actively
  feeding and reproducing
• Humans can serve as dead-end, accidental hosts or
  they can be a maintenance reservoir
• Controlling the vector controls the disease

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Characteristics of Arbovirus Infections

• Viral encephalitis
• brain, meninges, and spinal cord are involved
• convulsions, tremor, paralysis, loss of
  coordination, memory deficits, changes in speech
  and personality, coma
• survivors may experience permanent brain damage
• Treatment is supportive
• Vaccine for yellow fever, those traveling to
  tropics, those in high risk occupations

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N.A.Viruses

• Colorado tick fever (CTF)
• most common tick-borne viral fever in U.S.
• Rocky Mountain states
• Western equine encephalitis (WEE)
• western U.S. and Canada
• extremely dangerous to infants and small children
• Eastern equine encephalitis (EEE)
• eastern U.S. and Canada

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N.A. Viruses

• California encephalitis 2 different strains
• California strain
• western states
• little human impact
• LaCrosse strain
• eastern U.S. and Canada
• prevalent cause of viral encephalitis
• St. Louis encephalitis (SLE)
• most common of all in America
• epidemics in midwestern and southern states
• inapparent infections are very common

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N.A. Viruses

• West Nile encephalitis
• 1999
• 2000
• 2001

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Hemorrhagic Fevers

• Yellow fever
• eliminated in U.S.
• Two patterns of transmission
• urban cycle
• humans and mosquitoes, Aedes aegypti
• sylvan cycle
• forest monkeys and mosquitoes
• South America
• Acute fever, headache, muscle pain
• may progress to oral hemorrhage, nosebleed,
  vomiting, jaundice, and liver and kidney damage
• significant mortality rate

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Hemorrhagic Fevers

• Dengue fever
• flavivirus carried by Aedes mosquito
• not in U.S.
• usually mild infection
• dengue hemorrhagic shock syndrome, breakbone
  fever
• extreme muscle and joint pain
• can be fatal

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HIV and AIDS
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Retroviruses

• enveloped, ssRNA viruses
• encode reverse transcriptase enzyme which makes a
  DNA copy of their RNA genome
• Human Immunodeficiency Virus (HIV)
• cause of Acquired Immunodeficiency Syndrome
  (AIDS)
• HIV-1 HIV-2
• T-cell lymphotropic viruses I II - leukemia

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Epidemiology of HIV Infections

• Transmission occurs by direct and specific routes
• mainly through sexual intercourse and transfer of
  blood or blood products
• babies can be infected before or during birth,
  and from breast feeding
• HIV does not survive long outside of the body

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Facts.

• First nationally notifiable in 1984
• 6th most common cause of death among people aged
  25-44 years in the U.S.
• Men account for 70 of new infections
• IV drug abusers can be HIV carriers
• significant factor in spread to heterosexual
  population
• In 2006, the number of infected individuals
  worldwide is estimated to be 45 million
• 1 million in the U.S.

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Risk Categories

• homosexual or bisexual males 45
• intravenous drug users 30
• heterosexual partners of HIV carriers 11
• blood transfusions blood products since
  testing, no longer a serious risk
• inapparent or unknown risk 9 - (due to denial,
  death, unavailability)
• congenital or neonatal can be reduced with
  antiviral drugs
• medical dental personnel 1/500 needlestick

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Pathogenesis and Virulence Factors of HIV

• Enters through mucous membrane or skin
• travels to dendritic phagocytes beneath the
  epithelium
• multiplies and is shed
• Virus taken up and amplified by macrophages in
  the skin, lymph organs, bone marrow, and blood
• HIV attaches to CD4 and coreceptor
• HIV fuses with cell membrane
• Reverse transcriptase makes a DNA copy of RNA
• Viral DNA is integrated into host chromosome
  (provirus)
• Can produce a lytic infection or remain latent

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Effects of HIV infection

• Primary effects
• extreme leukopenia
• lymphocytes in particular
• formation of giant T cells and other syncytia
• allows the virus to spread directly from cell to
  cell
• Infected macrophages release the virus in central
  nervous system
• toxic effect, inflammation
• Secondary effects
• Destruction on CD4 lymphocytes
• allows for opportunistic infections and
  malignancies

115
Signs and Symptoms of HIV Infections and AIDS

• Initial infection
• mononucleosis-like symptoms that soon disappear
• Asymptomatic phase 2-15 years (avg. 10)
• Antibodies are detectable 8-16 weeks after
  infection
• When T4 cell levels fall below 200/mL AIDS
  symptoms appear

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Diagnosis of HIV Infection

• Testing based on detection of antibodies specific
  to the virus in serum or other fluids
• Initial screening
• ELISA
• rapid results but may result in false positives
• Follow up with Western blot analysis to rule out
  false positives
• False negatives can also occur
• persons who may have been exposed should be
  tested a second time 3-6 months later

117
Diagnosis of AIDS

• Made when a person meets the criteria
• Positive for the virus, and
• They fulfill one of the additional criteria
• They have a CD4 count of fewer than 200 cells/ml
  of blood
• Their CD4 cells account for fewer than 14 of all
  lymphocytes
• They experience one or more of a CDC-provided
  list of AIDS-defining illnesses

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Nonenveloped Nonsegmented ssRNA Viruses
119
Picornaviruses and Caliciviruses

• Picornaviruses
• Enterovirus poliovirus, HAV
• Rhinovirus - rhinovirus
• Cardiovirus
• Caliciviruses
• Norwalk agent (Norovirus) common cause of viral
  gastroenteritis (cruise ships)

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1. Poliovirus and Poliomyelitis

• naked capsid
• can survive stomach acids when ingested
• Poliomyelitis (polio)
• acute enteroviral infection of the spinal cord
• can cause neuromuscular paralysis
• Worldwide vaccination programs have reduced the
  number of cases
• eradication is expected

121
Hepatitis A Virus and Infectious Hepatitis

• Cubical picornavirus
• relatively resistant to heat and acid
• Not carried chronically
• principal reservoirs are asymptomatic, short-term
  carriers or people with clinical disease
• Fecal-oral transmission
• Most infections subclinical or vague, flu-like
  symptoms occur
• No specific treatment once the symptoms begin
• Inactivated viral vaccine
• Pooled immune serum globulin for those entering
  into endemic areas

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Human Rhinovirus (HRV)

• More than 110 serotypes associated with the
  common cold
• Sensitive to acidic environments
• optimum temperature is 33oC
• Unique molecular surface makes development of a
  vaccine unlikely
• Endemic with many strains circulating in the
  population at one time
• acquired from contaminated hands and fomites

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2. Caliciviruses

• Cruise ship virus
• Norwalk agent best known
• believed to cause 1/3rd of all viral
  gastroenteritis cases
• Transmitted by fecal-oral route
• Infection in all ages at any time of year
• Acute onset, nausea, vomiting, cramps, diarrhea,
  chills
• Rapid and complete recovery