Lesson 6.1

• DNA viruses of clinical significance

  • Type I - dsDNA
  • Type II - ssDNA
  • Type VII - dsDNA with RNA intermediate
• Type I - dsDNA

  • Adenoviridae
  • Herpesviridae
  • Poxviridae
  • Papovaviridae (Papillomaviridae and Polymaviridae)
• Type II - ssDNA

  • Parvoviridae
• Type VII - dsDNA with RNA intermediate

  • Hepadnaviridae
• Type I: Adenoviridae

  • Naked, icosahedral, dsDNA viruses
  • Has six subgenera (A-F), 49 serotypes (1-49)
  • most common serotypes: 1 to 8, 11, 21, 35, 37, and 40
  • Epidemiology: half of all infections are asymptomatic
  • 10%: pneumonia cases
  • 5-15%: gastroenteritis
  • occurs year-round in all age group
• Type I: Adenoviridae Clinical Manifestations

  • Respiratory tract infections (sero 3, 4, 7, 21)
  • Sero 14 - rare, causes severe to fatal ARD
  • Eye infections: Pharyngoconjunctival fever, major cause of viral conjunctivitis - epidemic keratoconjunctivitis (s. 8, 19), follicular conjunctivitis, "swimming pool conjunctivitis"
  • Gastroenteritis (sero 40, 41) - epidemic in children
  • Acute hemorrhagic cystitis (sero 11, 12)
  • lesser involvement in urinary tract, heart, CNS, liver, pancreas, genital tract
• Type I: Adenoviridae Diagnosis

  • EIA and commercial antigen detection kits: ID but not serotype
  • Culture: human embryonic kidney and many continuous cell lines
  • CPE: rounding and clustering of swollen cells (grape-like clusters)
  • ID via FA, EIA, molecular diagnostics
  • Serology: neutralization and hemagglutinin inhibition
  • EM used for epidemiologic studies, not routine
• Type I: Herpesviridae

  • enveloped, icosahedral, dsDNA viruses
  • known for causing latent and lifelong persistence in hosts
  • 8 species of human herpesviruses (HHV)
• 8 species of human herpesviruses (HHV)

  1. Herpes simplex virus type 1 (HSV-1) aka HHV-1
  2. Herpes simplex virus type 2 (HSV-2) aka HHV-2
  3. Varicella-zoster virus (VZV) aka HHV-3
  4. Epstein-Barr virus (EBV) aka HHV-4
  5. Cytomegalovirus (CMV) aka HHV-5
  6. HHV-6
  7. HHV-7
  8. HHV-8 aka Kaposi sarcoma herpesvirus
• Type I: Herpesviridae

  • Herpes Simplex Viruses
  • Causes very common infections: 80% of US adults (HSV1), 20% (HSV2)
  • Two main category of infections: Primary/initial/first and Recurrent/reactivation
  • Transmission: contact with contaminated secretions
  • Latency site: trigeminal ganglion and sacral ganglion
• Type I: Herpesviridae

  • Herpes Simplex Viruses
  • Oral herpes: primarily HSV-1: gingivostomatitis, herpes labialis ("fever blister" or "cold sore")
  • Genital herpes: HSV-2
  • Neonatal herpes: mother to infant transmission, mortality: 60% (treated); >70% (untreated)
• Type I: Herpesviridae

  • Herpes Simplex Viruses
  • Type of infections
  • HSV encephalitis: rare but high mortality (70%)
  • 20%: encephalitis cases
  • leading cause of fatal sporadic encephalitis
  • HSV-2 in neonates, HSV-1 in children and adults
  • Ocular herpes: keratitis - most common cause of corneal infection, blindness
  • Herpetic whitlow: skin/finger infections
• Type I: Herpesviridae

  • Herpes Simplex Viruses - Diagnosis
  • Optimal methods: antigen detection or virus isolation
  • Aspirates from vesicles, open lesions, host cells from infected sites
  • CSF culture usually unproductive
  • PCR may be used for CSF specimens
  • CPE may be seen within 24 hours (large rounded cells with foci)
  • human embryonic lung, rabbit kidney, Hep-2, A549
  • serotyped using monoclonal antibodies
  • Serology: may now be used for serotyping
  • Tzanck smear: Cowdry Type A bodies
• Type I: Herpesviridae

  • Varicella-Zoster Virus (VZV) aka HHV-3
  • Transmission: droplet inhalation or contact with infectious lesions
  • Epidemiology: 90% US adults have antibody to VZV
  • Clinical manifestations: Varicella (chickenpox) - very contagious primary infection, generally clinically apparent
  • Herpes zoster (shingles): reactivation occurs in 1 of 3 adults, latency site is dorsal root or cranial nerve ganglia, rash into vesicular lesions in unilateral dermatome pattern
  • Complication with aspirin: Reye's syndrome
• Type I: Herpesviridae

  • Varicella-Zoster Virus (VZV) aka HHV-3 Diagnosis
  • Characteristic clinical findings
  • Diagnosis is more difficult in atypical cases (immunosuppressed patients)
  • Fluorescent-labeled monoclonal antibodies and culture of fresh lesions/vesicles: human embryonic lung, vero cells, CPE occurs within 3-7 days
  • Tzanck smear: Cowdry Type A bodies
  • Vaccine: available; expected to produce life long immunity
• Type I: Herpesviridae

  • Epstein-Barr Virus (EBV) aka HHV-4
  • infects B cells via CR2/C3D receptor/CD21
  • causative agent of infective mononucleosis (IM) aka "kissing disease" or glandular fever
  • Epidemiology: 95% adults between 35-40, children that become infected, 35% EBV infection
  • recovered from oropharynx
  • Transmission: infected saliva
• Type I: Herpesviridae

  • Epstein-Barr Virus (EBV) aka HHV-4 - clinical manifestations
  • IM: sore throat, fever, lymphadenopathy, hepatomegaly, splenomegaly, general malaise
  • Complications: splenic hemorrhage and rupture, hepatitis, TTP with hemolytic anemia, Reye's syndrome, encephalitis, neurologic syndromes
  • Associated cancers: Burkitt lymphoma, Hodgkin disease, nasopharyngeal carcinoma
  • Important infectious agents in transplant recipients, causing B-cell lymphoma)
• Type I: Herpesviridae

  • Epstein-Barr Virus (EBV) aka HHV-4 - Diagnosis
  • Culture: requires human B lymphocytes
  • Serologic testing: Heterophile Abs: anti-sheep and anti-horse RBC's
  • May be screened by Paul-Bunnell heterophile Ab test, rapid test kits: EIA/Latex agglutination
  • EBV-specific antibodies
• EBV-specific antibodies

  • Anti-viral capsid antigen (Anti-VCA) -IgM, IgG
  • Antibody to early antigen (anti-EA) - IgG
  • Antibody to early antigen, diffuse (anti-EA/D) - IgG, IgA
  • Antibody to early antigen, restricted (anti-EA/R) - IgG
  • Antibody to EBV nuclear antigen (anti-EBNA)
• Type I: Herpesviridae

  • Cytomegalovirus (CMV) aka HHV-5
  • primarily infects WBCs in vivo
  • replicates only in human cells, slower than HSV and VZV
  • Transmission: close contact with infected person: saliva, tears, urine, stool, breastmilk
  • Sexual contact: semen, cervical/vaginal secretions
  • Blood and blood products
  • mother to infant - most common congenital infection (US), unlikely to occur if mother is sero-positive
• Type I: Herpesviridae

  • Cytomegalovirus (CMV) aka HHV-5 - clinical manifestations
  • most are asymptomatic
  • may manifest as self-limiting IM-like illness
  • immunocompromised: significant and life-threatening
  • Congenital: petechiae, hepatosplenomegaly, microcephaly, and chorioretinitis
  • Other manifestations: reduced birth weight, CNS involvement, mental impairment, deafness, death
  • CMV is one of leading causes of mental retardation, deafness, and intellectual impairment
• Type I: Herpesviridae

  • Cytomegalovirus (CMV) aka HHV-5
  • Culture: best from sterile body fluids (blood - buffy coat)
  • urine, respiratory secretions
  • CPE: large, round cells similar to HSV and VZV
  • isolated only using human diploid fibroblasts
  • replicates slowly: 3 weeks
  • Viral antigenemia test
  • PCR - preferred method for viral loads
  • blood donor screening
  • Congenital infection: first 2 weeks of life, urine
  • Serology not useful
• Type I: Herpesviridae

  • HHV-6
  • Common: ~95% of young adults are sero-positive
  • Variants A and B (possible cause of disease)
  • Persists in salivary glands: most likely transmission route via inhalation and close contact
  • isolated from stool
  • Clinical manifestations: childhood disease (roseola) aka 6th disease, roseola infantum, exanthem subitum, baby measles
  • Symptomatic: acute or febrile with maculopapular rash appearing as fever resolves, with 30-40% having seizures
  • reactivation of latent infections
• Type I: Herpesviridae

  • HHV-7
  • Infects T-lymphocytes via CD4 molecule; may also use other receptors and infects a broad range of host cells
  • shed in saliva of 75% of adults
  • also causes roseola
  • similar to HHV-6 but antibody protection is not inclusive
  • infection seems to occur later than HHV-6
  • most 2 y.o. are seronegative for HHV-7
  • most children are seropositive by 6 years
• Type I: Herpesviridae

  • HHV-8 aka Kaposi Sarcoma-Associated Herpesvirus
  • detected in all forms of Kaposi sarcoma
  • also play a role in the development of: primary effusion lymphomas and multicentric castleman disease
  • Transmission: NA and Europe - sexual contact; Africa and Mediterranean - casual contact
• Type I: Poxviridae

  • structurally largest (~300nm) and most complex virus family
  • Variola (smallpox): considered as one of the most important bioterrorism agens
  • Diseases caused: generally causes vesicular skin lesions in the host, small pox (Variola major); Alastrim (Variola minor); Cowpox (Vaccinia); Genital wart-like tumor (Molluscum contangiosum); monkeypox
  • Diagnosis: Pocks on chorioallantoic membrane of chicken embryos; Guarnieri bodies/inclusions (brightfield microscopy); brick-shaped virions (EM)
• Type I: Papovaviridae

  • Human Papilloma Virus (HPV)
  • of genus Papillomavius, family Papillomaviridae
  • agent of papillomas/warts
  • some are linked to cancer: cervical, oropharyngeal, laryngeal
  • more than 100 types: 40 are sexually transmitted: genital types, some leads to condylomata acuminata
  • 1-4 universally infects children and young adults (common and plantar warts) without significant consequences
• Type I: Papovaviridae

  • Polyomaviruses
  • associated with various diseases and malignancies
  • SV40 virus - associated with mesotheliomas, brain and bone tumors
  • BK virus - associated with renal diseases such as cystitis and nephropathy
  • JC virus - progressive multifocal leukoencephalopathy (PML)
• Type II: Parvoviridae

  • Parvovirus B19
  • Infects erythroid cells via the P antigen; also endothelial cells
  • naked, icosahedral, ssDNA viruses of family Parvoviridae (smallest DNA viruses), genus Erythrovirus
  • Clinical Manifestations: Erythema infectiosum aka fifth disease - most common; "slapped cheek" appearance of rash
  • Transient aplastic crisis - pure red cell aplasia or aplastic anemia
  • severe in immunocompromised individuals
  • Congenital: hydrops fetalis, miscarriages
• Type II: Parvoviridae

  • Human Bocavirus (HBoV)
  • novel parvovirus
  • causes upper respiratory tract illnesses
• RNA Viruses of Clinical Significance

  • Type III - dsRNA
  • Type IV - (+) ssRNA
  • Type V - (-) ssRNA
  • Type VI - ssRNA with DNA interm
• Type III - dsRNA

  • Reoviridae
• Type IV - (+) ssRNA

  • Astroviridae
  • Caliciviridae
  • Coronaviridae
  • Flaviviridae
  • Picornaviridae
  • Togaviridae
• Type V - (-) ssRNA

  • Arenaviridae
  • Bunyaviridae
  • Filoviridae
  • Orthomyxoviridae
  • Paramyxoviridae
  • Rhabdoviridae
• Type VI - ssRNA with DNA interm

  • Retroviridae
• Type III: Reoviridae

  • Rotavirus
  • Naked icosahedral dsDNA viruses
  • has two protein layer surrounding the capsid
  • wagon-wheel shaped under electron microscopy
  • transmission and tropism: fecal-oral route
  • replicates in the epithelial cells in the tips of microvilli of small intestine
  • shed in large quantities in the stool
• Type III: Reoviridae

  • Rotavirus
  • most common cause of infant and child gastroenteritis worldwide
  • "winter diarrhea"
  • Diagnosis: ELISA, latex agglutination tests, rapid membrane-bound colorimetric tests, electron microscopy of stool samples,
  • Vaccines: two types are currently available
• Type III: Reoviridae

  • Coltivirus
  • Arbovirus
  • Causative agent of Colorado-tick fever
  • causes dengue-like infection in western US and Canada
• Type III: Reoviridae

  • Orbivirus
  • Arbovirus
  • group of viruses that causes various diseases in various vertebrate animals and humans