Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a blood-borne virus that is
etiologically associated with Kaposi's sarcoma (KS), primary effusion lymphoma which is a
form of non-Hodgkin's lymphoma, and a subset of multicentric Castleman's disease which is a
lymphoproliferative disorder. The investigators developed serologic assays to measure
antibodies specific to KSHV latent and lytic antigens. Antibodies to KSHV antigens are found
in 70-100 percent of all clinical forms of KS patients. In contrast, relatively low
prevalence (2 to 5 percent) is found in the general population of North America.
Seroconversion is detected prior to KS onset in AIDS-KS patients, suggesting that primary
KSHV infection occurs predominantly in adulthood and is not ubiquitous. Antibody titers to
KSHV antigens remain elevated for years after seroconversion. The investigators have
recently found a 5 percent prevalence of KSHV infection in blood donors from San Antonio.
Further, KSHV has been found in the peripheral blood mononuclear cells (PBMC) of blood
donors, and organ transplantation and animal studies have provided evidence of likely
person-to-person transmission of KSHV. Thus, KSHV is a potential candidate for screening in
blood and plasma donors in view of its etiologic role for several malignancies, low but
appreciable prevalence in the general population, and lifelong persistence in a
cross-sectional study in blood donors from Texas.
The first aim of the study was to determine the prevalence of KSHV infection in blood donors
using specific KSHV serologic assays. The investigators used recently developed KSHV
specific serologic assays for detecting antibody to KSHV latent nuclear antigen, lytic
antigen, and orf65 (lytic antigen minor capsid protein) to determine the prevalence of KSHV
infection in a cross-sectional study of four representative blood banks in San Antonio,
Dallas, and Houston, Texas. A total of 500 random donors at each site were studied to detect
site-specific seroprevalence to plus or minus 2 percent with 95 percent confidence.
The second aim of the study was to analyze the demographic characteristics and the patterns
of other blood-borne infections of KSHV-seropositive blood donors. The cross-sectional study
in Houston and San Antonio was expanded to prospective study seroprevalence in a larger
population with questionnaire obtained demographic data to include gender, age, ethnicity,
education level, household income, and zip code. A total of 10,500 donors were obtained
from Houston. As the San Antonio center had the highest proportion of Hispanic donors, an
additional 2,000 donors were obtained and characterized demographically.
The third aim was to investigate KSHV molecular epidemiology in blood donors through
sequence determination of specific nested-polymerase chain reaction (PCR) and RT-PCR
products from peripheral blood mononuclear cells (PBMC) of KSHV-seropositive donors. The
2,000 blood samples from San Antonio were also used to amplify KSHV sequences from
peripheral blood mononuclear cells of KSHV positive donors using PCR, nested PCR and RT-PCR
with and without phorbol ester induction. Sequencing of amplified products was compared to
KSHV isolates from New York, Italy, England, and Africa for phylogenetic analysis and
assessment of diversity and distribution of KSHV strains in Texas. While the proposed
sampling represented only one center in Texas, comparison to isolates for New York and
abroad allowed determination of the likelihood that Texas strains were unique or imported
from Europe or Africa.
This regional project was performed in collaboration with the University Health System Donor
Center in San Antonio, BloodCare in Dallas, and Gulf Coast Regional Blood Center in Houston,
thus providing results for three separate metropolitan areas with rather different ethnic
compositions. These studies should provide valuable information to assess the necessity and
feasibility of national screening of blood donors for KSHV, and gain insight into the
patterns of infection as well as the diversity, the distribution, and the origins of the
virus strains in blood donors.
Observational Model: Natural History
University of Texas
United States: Federal Government