Longitudinal analysis of the humoral response to Kaposi's sarcoma-associated herpesvirus after primary infection in children.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS)-one of the most common pediatric cancers in sub-Saharan Africa-however, the factors that lead to disease progression are not fully understood. HIV infection, immunosuppression, and high KSHV viral load increase the risk of developing KS, suggesting that the loss of an effective anti-KSHV immune response may be an important risk factor. However, very little is known about the KSHV-specific immune response prior to KS and less is known about the anti-KSHV immune response during the very early stages of infection. We therefore prospectively followed a cohort of 86 Zambian children for 2 years after primary KSHV seroconversion to characterize the humoral immune response during the early stages of KSHV infection. Plasma, peripheral blood mononuclear cells, and oral swabs were collected from patients every 3 months and analyzed for KSHV-specific antibodies and presence of viral DNA. We observed an approximately 40% KSHV seropositive rate among infected children at time points after primary seroconversion, indicating that seroreversion is common after primary KSHV infection. At the time of primary KSHV seroconversion HIV-infected ART-naïve children had a more robust KSHV antibody response compared to HIV-infected children taking ART and HIV-uninfected children. Conversely, the longitudinal anti-KSHV antibody response was highly variable and did not correlate with available clinical information, HIV/ART status, or presence of KSHV DNA. Collectively, our data suggest that there is limited impact by the variations in the humoral immune response in young children after infection. J. Med. Virol. 88:1973-1981, 2016.