Virology

• Parvovirus B19 is pathogenic for humans and has a tropism for erythroid progenitor cells
• Human adeno-associated viruses (AAVs) are candidate vectors for gene therapy treatments
• Parvovirus virions contain two coat proteins, VP2 and VP1, with VP2 representing about 90% of virion protein
• Parvoviruses are the smallest DNA animal viruses
• Properties of parvoviruses

  • Autonomously replicating and defective parvoviruses that require a helper virus for replication
• There are two subfamilies of Parvoviridae: Parvovirinae (infect vertebrates) and Densovirinae (infect insects)
• Parvoviruses are highly dependent on cellular functions for replication, with viral DNA replication occurring in the nucleus
• The nonstructural protein NS1 is required for parvovirus replication, and viral replication results in cell death
• Parvovirus B19 causes erythema infectiosum (“Fifth disease”), polyarthralgia-arthritis syndrome in normal adults, aplastic crisis in patients with hemolytic disorders, chronic anemia in immunocompromised individuals, and fetal death
• Viral replication of parvoviruses is dependent on functions supplied by replicating host cells or by coinfecting helper viruses
• Parvovirus virions are extremely resistant to inactivation, stable between pH 3 and 9, withstand heating at 56°C for 60 minutes, but can be inactivated by formalin, β-propiolactone, and oxidizing agents
• Human parvovirus B19 infection targets immature cells in the erythroid lineage, with major sites of virus replication assumed to be the adult marrow, some blood cells, and the fetal liver
• The genome of parvoviruses is about 5 kb, linear, single-stranded DNA
• Human B19 parvovirus primarily infects primary erythroid progenitors, and the cellular receptor for B19 is blood group P antigen (globoside)
• Parvoviruses must infect dividing cells as they do not have the ability to stimulate resting cells to initiate DNA synthesis
• Genera within Parvovirinae

  • Erythroparvovirus (includes human parvovirus B19), Bocaparvovirus (includes human bocaviruses), Protoparvovirus (includes feline panleukopenia virus and canine parvovirus), Dependovirus (contains defective viruses that depend on a helper virus)
• Major sites of virus replication in patients are assumed to be the adult marrow, some blood cells, and the fetal liver
• Bone marrow biopsies from infected patients show erythrocyte maturation arrest, with erythroblast intranuclear inclusions
• In cases of fetal death, chronic infections may have caused severe anemia in the fetus
• Diseases caused by human parvovirus B19


  • Several diseases
• B19 can be found in blood and respiratory secretions of infected patients
• The pathogenesis of human bocavirus infection is not yet known, though some studies have associated its presence with respiratory disease
• Plasmaderived clotting factor concentrates are screened for the presence of B19 DNA due to its resistance to harsh treatments
• Both virus-specific immunoglobulin M (IgM) and IgG antibodies are made after B19 infections
• Persistence of low levels of B19 DNA has been detected in blood, skin, tonsil, liver, and synovial tissues of immunocompetent persons
• No evidence of virus excretion in feces or urine
• Erythema infectiosum is most common in children of early school age and occasionally affects adults
• Parvoviruses have been found contaminating laboratory reagents due to their highly stable nature
• Joint involvement due to immune complex deposition is a prominent feature in adult cases of erythema infectiosum
• The incubation period of erythema infectiosum is usually 1–2 weeks but may extend to 3 weeks
• Virus is present in nasal washes and gargle specimens during viremia, identifying the upper respiratory tract as the site of viral shedding
• The prevalence of antibodies to B19 is higher among people with hemophilia than the general population
• Immature cells in the erythroid lineage are principal targets for human B19 parvovirus
• In immunocompromised patients, persistent B19 infections occur, resulting in chronic anemia
• Persistent parvovirus infections occur in patients with immune deficiencies who fail to make virus-neutralizing antibodies, resulting in anemia
• Viral replication

  Causes cell death, interrupting red blood cell production
• The rash associated with erythema infectiosum is at least partly immune complex mediated
• Known parvovirus diseases reflect target specificity as nondefective parvoviruses require dividing host cells to replicate
• Transmission of B19 is presumably by the respiratory route
• B19 can be transmitted parenterally by blood transfusions or by infected blood products and vertically from mother to fetus