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

Abstract

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. © 2016 Wiley Periodicals, Inc.

Establishment of Tree Shrew Animal Model for Kaposi’s Sarcoma-Associated Herpesvirus (HHV-8) Infection

“…In this study, all animals were regularly monitored for clinical signs and symptoms throughout the experiment period. They developed an intermittent and transient type of infection similar to phenomena reported in different populations ( Olp et al, 2016 ). Further, we used RT-PCR to detect mRNA levels in the peripheral blood samples.…”

Kaposi sarcoma

“…Systemic analysis of antibodies to all KSHV proteins showed that ORF38, ORF61, ORF59 and K5 elicited detectable responses in individuals with KSHV-associated diseases 110 . However, antibodies to KSHV are rarely neutralizing 111 .…”

Longitudinal quantification of adenovirus neutralizing responses in Zambian mother-infant pairs: Impact of HIV-1 infection and its treatment

“…Children in SSA, and elsewhere, are often exposed to infectious diseases at a young age, which makes infant vaccination crucial for effective disease control and child well-being and development. Indeed, our lab and others have demonstrated that seroconversion to Kaposi's Sarcoma Herpesvirus (KSHV) occurs in sub-Saharan infants at levels near the adult prevalence by 4 years of age [37,38]. Using adenoviruses as a vaccine vector has been shown to elicit strong T and B cell responses to inserted transgenes and could also confer immunity to the Ad used as the backbone, thereby decreasing the burden of adenovirus associated diseases in young children.…”