Little is known about factors that determine seminal shedding of human immunodeficiency virus type 1 (HIV), human cytomegalovirus (CMV), and human herpes virus type 8 (HHV-8). Our long-term goals are to delineate the anatomic sites and factors determining viral shedding, to develop strategies to lower the viral burden in semen, and, consequently, to reduce sexual transmission.
Specific Aim 1 : To determine the anatomic sites of viral infection and replication in the male genital tract. We will test the hypotheses that the prostate gland and urethra are critical viral reservoirs and that these sites remain reservoirs in HIV-infected men receiving highly active anti-retroviral therapy (HAART) by localizing and quantifying viral RNA and DNA in systematic prostate biopsies, urethral secretions, expressed prostatic secretions, and ejaculated semen. These data will increase our understanding of the biology of sexual transmission and the potential of therapy to reduce genital trac viral reservoirs in the male.
Specific Aim 2. To examine mechanisms of viral-viral interaction that facilitate seminal virus shedding. We will test the hypothesis that expression of one genital virus can up-regulate expression and shedding of other genital tract viruses by investigating the effects of anti-CMV therapy on HIV, HHV-8, or CMV burden, including CMV-induced expression of chemokines and chemokine receptors in HIV-permissive cells that may activate latent infection or up-regulate low levels of HIV gene expression. These studies are important because coinfection with multiple genital viruses is common. Thus, controlling one genital tract virus may limit viral-viral interactions, reduce the viral burden in semen, and decrease the sexual transmission of other viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK057810-02
Application #
6381826
Study Section
Special Emphasis Panel (ZRG1-UROL (01))
Program Officer
Rankin, Tracy L
Project Start
2000-09-15
Project End
2005-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$362,574
Indirect Cost
Name
University of Washington
Department
Urology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kumari, Daman; Biacsi, Rea Erika; Usdin, Karen (2011) Repeat expansion affects both transcription initiation and elongation in friedreich ataxia cells. J Biol Chem 286:4209-15