Humoral immune response to Kaposi's sarcoma-associated herpesvirus in persons with and without Kaposi's sarcoma

Humoral immunity to herpesvirus infections is influenced by both the nature of the antibodies involved and the antigenic determinants that elicit these responses. In general, antibodies which block viral infectivity, i.e. neutralizing antibodies, have been the antibodies most associated with either prevalence of infection or resolution of a viral infection. Little is known about neutralizing antibodies to the recently discovered gamma herpesvirus, KSHV. While increased anti-KSHV antibodies are found in persons known to manifest clinical Kaposi's sarcoma (KS), the functionality of anti-KSHV antibodies and the role they impart to KSHV-associated disease syndromes has not been investigated. In this dissertation, I evaluated whether neutralizing antibodies play a role in KS disease progression using a neutralizing antibody assay which utilizes a replication competent recombinant virus expressing the green fluorescent protein (GFP) developed as a part of this research. Three specific aims of this research were: (1) can neutralizing antibody titers in KS subjects be documented; (2) are there differences among cohorts of KS subjects to neutralize KSHV; and (3) is disease status correlated with the presence of antibodies? A cross sectional study of serum samples from 92 HIV infected and uninfected subjects with and without KS were compared for the presence and functional ability of neutralizing antibodies. Neutralizing antibody titers were significantly lower among subjects with KS compared with subjects infected with KSHV but with no clinical evidence of disease. These observations suggest that neutralizing antibodies could play an important role in KS disease progression. To further examine the role between neutralizing antibodies and disease progression, a longitudinal study of three time points from 34 HIV infected subjects with and without clinical KS was examined. The trend in neutralizing antibody titers and of CD4 counts over time did not appear to differ significantly between subjects with clinical KS or subjects without clinical KS. Unlike the results of the cross sectional study, these results do not indicate a correlation of neutralizing antibodies and KS disease progression. Further studies will be required to evaluate the discrepancy between these two studies and to definitively evaluate the role neutralizing antibodies play in the pathogenesis of KSHV.