Viral Diseases

1
Viral Diseases
2
Poxviruses

• Smallpox (Variola)
• Smallpox virus (Orthopox virus)
• Variola major has 20 mortality
• Variola minor has lt1 mortality
• Monkeypox
• Prevention by smallpox vaccination

Figure 21.9
3
Herpesviruses

• Varicella-zoster virus (Human herpes virus 3)
• Transmitted by the respiratory route
• Causes pus-filled vesicles
• Virus may remain latent in dorsal root ganglia

Figure 21.10a
4
Shingles

• Reactivation of latent HHV-3 releases viruses
  that move along peripheral nerves to skin.

Figure 21.10b
5
Herpes simplex 1 and Herpes simplex 2

• Human herpes virus 1 and HHV-2
• Cold sores or fever blisters (vesicles on lips)
• Herpes gladiatorum (vesicles on skin)
• Herpes whitlow (vesicles on fingers)
• Herpes encephalitis (HHV-2 has up to a 70
  fatality rate)
• HHV-1 can remain latent in trigeminal nerve
  ganglia
• HHV-2 can remain latent in sacral nerve ganglia
• Acyclovir may lessen symptoms

6
Measles (Rubeola)

• Measles virus
• Transmitted by respiratory route
• Macular rash and Koplik's spots
• Prevented by vaccination
• Encephalitis in 1 in 1000 cases
• Subacute sclerosing panencephalitis in 1 in
  1,000,000 cases

Figure 21.14
7
Rubella (German Measles)

• Rubella virus
• Macular rash and fever
• Congenital rubella syndrome causes severe fetal
  damage
• Prevented by vaccination

Figure 21.15
8

• A 1905 list of skin rashes included 1-measles,
  2-scarlet fever, 3-rubella, 4-Filatow-Dukes
  (mild scarlet fever), and 5-
• Fifth Disease
• Human parvovirus B19 produces milk flu-like
  symptoms and facial rash
• Roseola
• Human herpesvirus 6 causes a high fever and rash,
  lasting for 1-2 days

9
Poliomyelitis

• Poliovirus
• Transmitted by ingestion
• Initial symptoms sore throat and nausea
• Viremia may occur if persistent, virus can enter
  the CNS destruction of motor cells and paralysis
  occurs in lt1 of cases
• Prevention is by vaccination (enhanced-inactivated
  polio vaccine)

10
Poliomyelitis
Figure 22.10
11
Rabies virus (Rhabdovirus)

• Transmitted by animal bite
• Virus multiplies in skeletal muscles, then brain
  cells causing encephalitis
• Initial symptoms may include muscle spasms of the
  mouth and pharynx and hydrophobia
• Furious rabies animals are restless then highly
  excitable
• Paralytic rabies animals seem unaware of
  surroundings
• Preexposure prophylaxis Infection of human
  diploid cells vaccine
• Postexposure treatment Vaccine immune globulin

12
Arboviral Encephalitis

• Arboviruses are arthropod-borne viruses that
  belong to several families.
• Prevention is by controlling mosquitoes

13
Burkitts Lymphoma

• Nasopharyngeal carcinoma
• Epstein-Barr virus (Human herpesvirus 4)
• Cancer in immunosuppressed individuals, and
  malaria and AIDS patients

14
Infectious Mononucleosis

• Epstein-Barr virus (Human herpesvirus 4)
• Childhood infections are asymptomatic
• Transmitted via saliva
• Characterized by proliferation of monocytes

15
Cytomegalic Inclusion Disease

• Cytomegalovirus (Human herpesvirus 5)
• Infected cells swell (cyto-, mega-)
• Latent in white blood cells
• May be asymptomatic or mild
• Transmitted across the placenta, may cause mental
  retardation
• Transmitted sexually, by blood, or by
  transplanted tissue

16
Viral Hemorrhagic Fevers
17
Viral Pneumonia

• Viral pneumonia as a complication of influenza,
  measles, chickenpox
• Viral etiology suspected if no cause determined
• Respiratory Syncytial Virus (RSV)
• Common in infants 4500 deaths annually
• Causes cell fusion (syncytium) in cell culture
• Symptoms coughing
• Diagnosis by serologic test for viruses and
  antibodies
• Treatment Ribavirin

18
Influenza

• Chills, fever, headache, muscle aches (no
  intestinal symptoms)
• 1 mortality due to secondary bacterial
  infections
• Treatment Amantadine
• Vaccine for high-risk individuals

19
Influenza

• Hemagglutinin (H) spikes used for attachment to
  host cells (15)
• Neuraminidase (N) spikes used to release virus
  from cell (9)
• Classified by H and N spike antigens

20
Influenza

• Antigenic shift
• Changes in H and N spikes
• Probably due to genetic recombination between
  different strains infecting the same cell
• Antigenic drift
• Mutations in genes encoding H or N spikes
• May involve only 1 amino acid
• Allows virus to avoid mucosal IgA antibodies

21
Mumps

• Mumps virus
• Enters through respiratory tract
• Infects parotid glands
• Prevented with MMR vaccine

Figure 25.14
22
Hepatitis

• Inflammation of the liver
• Hepatitis may result from drug or chemical
  toxicity, EB virus, CMV, or the Hepatitis viruses

23
Hepatitis
Table 25.1
24
Viral Gastroenteritis

• Rotavirus
• 3 million cases annually
• 1-2 day incubation, 1 week illness
• Norovirus
• 50 of U.S. adults have antibodies
• 1-2 day incubation. 1-3 day illness
• Treated with rehydration

Figure 25.17
25
Genital Herpes

• Herpes simplex virus 2 (Human herpesvirus 2) or
  HHV 2
• Neonatal herpes transmitted to fetus or newborns
• Recurrences from viruses latent in nerves
• Suppression acyclovir or valacyclovir

26
Genital Warts

• Human papillomaviruses
• Treatment Imiquimod to stimulate interferon
• HPV 16 causes cervical cancer and cancer of the
  penis
• DNA test to detect cancer-causing strains
• Vaccination against HPV strains

27
Human Immunodeficiency Virus

• HIV is retrovirus RNA virus that makes DNA from
  RNA template
• Increased number of cases began in 1981, virus
  was identified in 1983
• HIV is enveloped virus that infects CD4
  lymphocytes (T helper cells)
• Envelope spikes (gp120) attach to CD4 receptors

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Figure 19.12a
29
HIV Infection
Figure 19.12b
30
HIV Infection
Capsid
Reverse transcriptase
DNA
Virus
Two identical stands of RNA
1
Retrovirus penetrates host cell.
Host cell
DNA of one of the host cells chromosomes
5
Mature retrovirus leaves host cell, acquiring an
envelope as it buds out.
Reverse transcriptase
2
Virion penetrates cell and its RNA is uncoated
DNA is produced
Viral RNA
Identical strands of RNA
4
Transcription of the provirus may also occur,
producing RNA for new retrovirus genomes and RNA
that codes for the retrovirus capsid and envelope
proteins.
Viral proteins
RNA
3
The new viral DNA is transported into the host
cells nucleus and integrated as a provirus. The
provirus may divide indefinitely with the host
cell DNA.
Provirus
Figure 13.19
31
HIV Infection
Figure 19.13
32
HIV Infection

• HIV may produce latent infections and remain
  dormant for years
• HIV may remain in DNA of host cell
• HIV may be produced, but remain in vacuoles
• Antibodies cannot detect latent infections
• 5 do not progress to AIDS
• HIV produces many mutations and antigenic
  variation
• HIV may cause cell fusion to allow virus to move
  between cells

33
Stages of Disease

• Category A no symptoms or swollen lymph glands
• Category B persistent infection with Candida
  albicans, other infections and cancerous or
  precancerous conditions
• Category C clinical AIDS Candida in lower
  respiratory tract, cytomegalovirus of eye,
  Pneumocystis pneumonia, toxoplasmosis of the
  brain and Kaposis sarcoma

34
T cell Counts

• Normal T cell level is 800-1000 cells/mm3
• Below 200 CD4 Tcells/mm3 is diagnostic of AIDS
• Progression of disease takes about 10 years in
  US 5 years in Africa
• 108 HIV produced/day
• CD4 T cells killed in 2 days (normally survive
  for years)
• Loss of T cells may be 20 million/day
• Body is unable to replenish cells

35
HIV Transmission

• HIV survives 6 hours outside a cell
• HIV survives gt1.5 days inside a cell
• Infected body fluids transmit HIV via
• Sexual contact
• Breast milk
• Transplacental infection of fetus
• Blood-contaminated needles
• Organ transplants
• Artificial insemination
• Blood transfusion

36
Diagnostic Methods

• Seroconversion takes up to 3 months
• HIV antibodies detected by ELISA
• HIV antigens detected by Western blotting
• Plasma viral load is determined by PCR or nucleic
  acid hybridization

37
Prions

• Infectious proteins
• Inherited and transmissible by ingestion,
  transplant, surgical instruments
• Spongiform encephalopathies Sheep scrapie,
  Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Sc
  heinker syndrome, fatal familial insomnia, mad
  cow disease
• PrPC, normal cellular prion protein, on cell
  surface
• PrPSc, scrapie protein, accumulate in brain cells
  forming plaques