Comparative analysis of parvovirus B19 persistence and development of anti-non-structural protein-1 antibodies in the development of parvovirus B19 arthropathy

Parvovirus B19 (B19) is a non-enveloped, single-stranded DNA virus in the family Parvoviridae. The B19 capsid is composed of two structural proteins, VP1 and VP2, which contain multiple epitopes that are recognized by virus-neutralizing antibodies. The major non-structural protein, NS-1, is vital for viral replication and is also toxic to host cells. The most common clinical sequelae of B19 infection is erythema infectiosum (EI) which is characterized by fever, 'flu'-like symptoms, and a rash on the face and torso. Fifty percent of B19-infected adults experience acute arthropathy (arthritis and/or arthralgia) lasting up to 1 month. Of these individuals, 20% will develop chronic arthropathy (lasting more than one month and persisting from months to years). This thesis examines the hypothesis that B19 persistence and the presence of anti-NS-1 antibodies in peripheral blood are correlated with the development of B19 infection-associated arthropathy, and that the development of anti-NS-1 antibodies is dependent upon B19 persistence. A study of the possible associated factors leading to B19 arthropathy may help in the diagnosis of this condition and serve to provide insights into its pathogenesis. B19 PCR and NS-1 immunoblot were used to examine the prevalence of B19 persistence (presence of B19 DNA) and anti-NS-1 antibodies in peripheral blood samples from a cohort of individuals with recent B19 infections. Potential differences in these parameters were investigated between subjects who developed and did not develop arthropathy. Subjects with histories of past, undocumented B19 infections were also tested to determine the population incidence of peripheral blood B19 persistence and anti-NS-1 antibodies. Differences in the occurrence of B19 DNA and anti-NS-1 between recent and past-infected groups would indicate changes in these parameters over time. Finally, the effects of re-exposure to active B19 on the population frequency of peripheral blood B19 DNA and anti-NS-1 were examined in subjects with past undocumented B19 infections. Results indicate that the presence of B19 DNA in peripheral blood was not related to the development of acute or chronic arthropathy following B19 infection. Instead, the ability to detect peripheral blood B19 DNA was correlated with the amount of time that had passed following B19 infection (an indirect indicator of the development of immunity to B19). A possible accelerated clearance of B19 from peripheral blood after infection was observed in subjects who did not develop arthropathy following B19 infection. It was hypothesized that this accelerated immune response may prevent formation of soluble immune complexes that are believed to mediate acute B19 arthropathy. The role that a delay in B19 clearance has on the development of chronic B19 arthropathy is unknown. In addition, anti-NS-1 antibodies were not found to be related to B19 persistence or the development of B19 arthropathy. Instead, anti-NS- 1 antibodies were found to be indicators of past B19 infection in certain individuals. It was hypothesized that the development of anti-NS-1 was due to high initial B19 viremia related to prolonged or repeated exposure to B19. Finally, a transient boost in the incidence of peripheral blood B19 DNA and anti-NS-1 antibodies in subjects re-exposed to B19 indicate that subclinical reinfection with B19 may occur.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat