Kaposi's Sarcoma-associated herpesvirus is transmitted primarily by saliva, though other routes including semen and breastmilk have also been described. There exists a big discrepancy in KSHV seroprevalence across different populations. It is less than 10% in the US, but > 50% in KSHV endemic regions in Sub-Saharan Africa. Whereas the US AIDS-KS epidemic was driven by repeated contact among MSM, in endemic regions KSHV is acquired in childhood. We are responding to RFA-CA-18- 013 to decipher how KSHV is transmitted. The overall goal of this application is to understand the transmission of KSHV in molecular terms, with the ultimate goal being to inform vaccine design and identify other means of disrupting transmission. To achieve this goal, we will investigate the three pillars of transmissibility of infectious agents: (i) variance among KSHV strains using existing specimens from large clinical cohorts, (ii) variance among the innate immune responses to KSHV infection, and (iii) variance in the microbiome which may affect both KSHV itself (as measured by local viral load) and the innate immune response to infection. In each case, we will start by profiling natural human variation and then explore the function of significant viral and host variants in functional assays for entry, replication and transmission.

Public Health Relevance

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is transmitted by saliva, though other routes include bodily fluids. We are responding to RFA-CA-18-013 to decipher how KSHV is transmitted. The overall goal of this application is to understand the transmission of KSHV in molecular terms, with the ultimate goal being to inform vaccine design and identify other means of disrupting transmission. To achieve this goal, we will investigate the variance among KSHV strains using existing specimens from large clinical cohorts, variance among the innate immune responses to KSHV infection, and variance in the microbiome.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA239583-02
Application #
9896795
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
2019-05-01
Project End
2024-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599