Naked DNA Viruses: Parvoviridae

• Naked DNA viruses lack an envelope

Naked DNA Virus Families

• Parvoviridae
• Adenoviridae
• Papillomaviridae

Parvoviridae

• Parvoviruses are the smallest DNA animal viruses
• Parvovirus B19 is pathogenic for humans and has a tropism for erythroid progenitor cells
• Parvovirus B19 can cause:
  • Erythema infectiosum ("Fifth disease"), a common childhood exanthem
  • Polyarthralgia-arthritis syndrome in normal adults
  • Aplastic crisis in patients with hemolytic disorders
  • Chronic anemia in immunocompromised individuals
  • Fetal death

Parvovirus Characteristics

• Belongs to the Family Parvoviridae
• Icosahedral and nonenveloped particles
• Virions are resistant to inactivation and stable between pH 3 and 9
• Virions can withstand heating at 56°C for 60 minutes, but are inactivated by formalin, β-propiolactone, and oxidizing agents
• Virions contain two coat proteins, VP1 and VP2
  • VP2 is the major capsid protein, representing about 90% of the virion protein
• The genome has linear, single-stranded DNA
• Virion diameter is 18-26 nm, with 32 capsomeres
• Composition is 20% DNA and 80% protein
• Viral replication occurs in the nucleus, dependent on functions of dividing host cells
• Has a tropism for red blood cell progenitors, and is environmentally stable.
• Immature cells in the erythroid lineage are principal targets for human B19 parvovirus, with primary erythroid progenitors known to be permissive for B19 infection
• The cellular receptor for B19 is blood group P antigen (globoside), expressed on mature erythrocytes, erythroid progenitors, megakaryocytes, endothelial cells, placenta, and fetal liver and heart
• Major sites of virus replication are the adult marrow, some blood cells, and the fetal liver
• Viral replication causes cell death and interrupts red blood cell production, occurring in the nucleus
• The nonstructural protein, NS1, is needed for replication
• B19 can be found in blood and respiratory secretions of infected patients, typically transmitted via the respiratory route
• The virus can be transmitted parenterally through blood transfusions or infected blood products and vertically from mother to fetus

Fifth Disease

• Erythema infectiosum is the most common manifestation of human parvovirus B19 infection
• Erythematous illness commonly affects children of early school age, and occasionally affects adults
• Fever and mild constitutional symptoms may accompany the rash
• Rash has a typical "slapped cheek" appearance
• Joint involvement due to immune complex deposition is a prominent feature in adult cases, affecting the hands and knees most frequently

Adenoviridae

• Icosahedral symmetry with a capsid composed of 252 capsomeres and lacks an envelope
• A "fiber" projects from each of the 12 vertices or penton bases
• The rest of the capsid is composed of 240 hexon capsomeres
• Hexons, pentons, and fibers constitute the major adenovirus antigens important in viral classification
• The DNA genome is linear and double-stranded
• GC content of the DNA is lowest (48-49%) in group A (types 12, 18, and 31) adenoviruses, the most strongly oncogenic types
• Virion diameter is 70-90 nm, with 252 capsomeres, and fiber projections from each vertex
• Composition is 13% DNA and 87% protein
• Double-stranded DNA, linear, 26-45 kbp, protein bound to termini, and infectious
• Important antigens (hexon, penton base, fiber) are associated with the major outer capsid proteins
• Replication occurs in the Nucleus
• Excellent models for molecular studies of eukaryotic cell processes
• Human adenoviruses are divided into seven groups (A-G) based on genetic, physical, chemical, and biologic properties
• Adenoviruses of a given group have fibers of a characteristic length and display considerable DNA homology encoding structural proteins (>85%, compared with <20% to members of other groups)
• They exhibit similar capacities to agglutinate erythrocytes from either monkeys or rats
• Viruses within a group tend to behave similarly with respect to epidemiologic spread and disease association
• Cause infections in epithelial cells of the respiratory tract, eye, gastrointestinal tract, and urinary tract

Adenovirus Types and Clinical Significance

• 12, 18, and 31: Oncogenic
• Group C viruses (1, 2, and 5): Respiratory symptoms in infants and children
• 3, 4, and 7: Respiratory symptoms in adolescents and adults (military camps)
• 3, 7, and 21: Childhood pneumonia
• 3 and 7: Pharyngoconjunctival fever in children (swimming pool conjunctivitis), especially in children's summer camps
• 8, 19, and 37: Epidemic keratoconjunctivitis in adults
• 40 and 41: Infantile gastroenteritis in children (retrieved from stool samples)
• Spread by direct contact, the fecal-oral route, respiratory droplets, or contaminated fomites
• Infections with types 1, 2, 5, and 6 occur chiefly during the first years of life; types 3 and 7 are contracted during school years
• Types 4, 8, and 19 may not be encountered until adulthood
• Respiratory disease caused by types 3, 4, and 7 is common among military recruits and young adults in group or institutional settings
• Eye infections can be transmitted in several ways, with hand-to-eye transfer being particularly important
• Swimming pool conjunctivitis outbreaks are presumably waterborne, and usually occur in the summer
• Epidemic keratoconjunctivitis is a highly contagious and serious disease
• Infections can be prevented by hand washing
• Environmental surfaces can be disinfected with sodium hypochlorite, and paper towels may be advisable in group settings
• The risk of waterborne outbreaks of conjunctivitis can be minimized by chlorination of swimming pools and waste water
• Strict asepsis during eye examinations, coupled with adequate sterilization of equipment, is essential for the control of epidemic keratoconjunctivitis

Papillomaviridae

• Naked viruses with double-stranded circular DNA and an icosahedral nucleocapsid
• Oncogenic
• Virion is icosahedral, 55 nm in diameter
• Composition is 10% DNA and 90% protein
• Genome is double-stranded DNA, circular, 8 kbp
• Contains two structural proteins, with cellular histones that condense DNA in virion
• No envelope
• Replication occurs in the nucleus
• Stimulate cell DNA synthesis, have restricted host range and tissue tropism and is a significant cause of human cancer, especially cervical cancer
• Viral oncoproteins interact with cellular tumor suppressor proteins
• Transmission of viral infections occurs by close contact
• Papillomaviruses cause infections at cutaneous and mucosal sites, sometimes leading to warts
• Different kinds of warts include:
  • Skin warts
  • Plantar warts
  • Flat warts
  • Anogenital warts
  • Laryngeal papillomas
• Several cancers can be caused by infection, like:
  • Cancers of the cervix
  • Vulva
  • Penis and anus
  • A subset of head and neck cancers
• Human Papilloma Virus (HPV) is highly tropic for epithelial cells of the skin and mucous membranes
• Viral nucleic acid is found in basal stem cells, but late gene expression (capsid proteins) is restricted to the uppermost layer of differentiated keratinocytes
• HPV-16 and HPV-18 are responsible for more than 70% of all cervical cancers, with type 16 being most common
• Anal cancer is associated with high-risk HPV infection
• Immunocompromised patients are especially at risk, as are men who have sex with men. Multiple HPV types have been commonly found in the anal canals of HIV-infected men
• Oropharyngeal cancers, a subset of head and neck squamous cell carcinomas, are also linked to HPV infections, especially by type 16
• Anogenital warts are usually (90%) caused by low-risk HPV types 6 and 11
• Laryngeal papillomas in children, also called recurrent respiratory papillomatosis, are caused by HPV-6 and HPV-11, the same viruses that cause benign genital condylomas
• The infection is acquired during passage through the birth canal of a mother with genital warts
• Widespread use of the Papanicolaou (Pap) smear for cervical cancer detection has led to substantial decrease in deaths due to cervical cancer, as this test aims to detect precancerous cellular changes in morphology, allowing for lesion removal prior to cancer development

HPV Vaccines

• Nonavalent vaccine – protects against types 6,11,16,18,31,33,45,52,58
• Quadrivalent vaccine – protects against types 6, 11, 16 and 18
• Bivalent vaccine protects against 16 and 18
• The WHO recommends HPV vaccination for all girls 9 to 14 years old, ideally administered before sexual debut (i.e., before risk of first exposure to HPV infection)