Biological Sciences, School of
Date of this Version
8-2015
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent for all forms of Kaposi’s sarcoma (KS)—one of the most common pediatric cancers in sub-Saharan Africa during the AIDS epidemic. KS was endemic in sub-Saharan Africa prior to the HIV/AIDS epidemic, but KS cases drastically increased thereafter. Our laboratory previously observed that KSHV infection is common among Zambian children and saliva is the major route of transmission. However, additional factors associated with the transmission of KSHV to children are poorly understood. Since a vaccine against KSHV is not currently available, it is paramount to understand factors associated with transmission so that alternative strategies can be developed to prevent KSHV acquisition during early childhood.
The studies reported here reveal that early childhood transmission of KSHV is multifactorial. We show that household members served as primary KSHV transmission sources to children, but transmission from outside the household also occurred. We also describe a prospective cohort study—that followed HIV-exposed, KSHV-negative children—to assess the impact of HIV and antiretroviral therapy (ART) on risk of KSHV acquisition. Data from this cohort suggest that early ART and prevention of immune suppression significantly reduce the risk of KSHV acquisition among HIV-infected children. After primary KSHV infection, however, KSHV antibody titer was highly variable and did not correlate with available clinical information, HIV/ART status, or KSHV DNA detection.
Additionally, next-generation deep sequencing was used to examine KSHV genomic diversity in an endemic setting as the first step to investigate the possible impact of genetic variations on pathogenesis and transmission. We detected distinct phylogenetic clustering between KSHV isolates from Zambia and Western countries, and identified four genes with unprecedented levels of polymorphisms.
The results described herein present a deeper understanding of epidemiological, immunological, and viral factors that may be related to KSHV transmission among young children in Zambia—a region where KSHV is endemic and HIV is epidemic. The findings from this study will be important for developing public health strategies to reduce KSHV spread among young children. This, in turn, will help reduce the burden of KS among children and adults in endemic settings.
Adviser: Charles Wood
Comments
A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Biological Sciences (Microbiology and Molecular Biology), Under the Supervision of Professor Charles Wood. Lincoln, Nebraska: August, 2015
Copyright (c) 2015 Landon N. Olp