Heather Watts, PhD - US grants

While persistent HSV infection has long been recognized as an opportunistic infection in HIV-infected persons, little is known of the natural history of this infection. Serologic evidence of HSV-2 is seen in 40-90% of HIV-1 infected persons and HSV-2 strains that are acyclovir and foscarnet resistant are being reported with increasing frequency. Our preliminary data suggest that HIV-infected persons shed HSV on 10% of all days sampled; a rate 10 times greater than HIV negative persons. 60% of these reactivations are subclinical. HIV-infected pregnant women reactivate HSV at delivery up to 4 times more than HIV-negative women, potentially exposing their infant to the acquisition of neonatal herpes. We have detected HIV-1 in rectal secretions of 22% of subjects with frequent HSV-2 rectal reactivation, suggesting that subclinical HSV shedding may enhance the transmission of HIV. The specific aims of this proposal are to 1) To define the natural history of symptomatic and subclinical reactivation of HSV in HIV-infected persons by defining the anatomic sites, frequency, and duration of symptomatic and subclinical reactivation of HSV among persons co-infected with HSV and HIV. Also, to determine if higher rates of reactivation in HIV seropositive vs HIV seronegative persons are related to differences in viral titer, local host responses, or both. 2) To evaluate the interrelationship between HSV reactivation and HIV replication on mucosal surfaces by determining a) if HSV reactivation increases the frequency and titer of HIV found in rectal secretions and cervical secretions, b) whether genital HSV reactivations at delivery increase the amount of HIV the newborn is exposed to at deliver, and c) if suppression of HSV reactivation will decrease HIV replication on mucosal surfaces. To achieve these objectives, a cohort of HIV-infected men and women will be prospectively followed for evidence of subclinical HSV infection by viral isolation and HSV and HIV DNA and RNA PCR assays. These studies, in concert with those in Projects I, II and IV provide a unique opportunity to study the biology of HSV reactivation and its role as a cofactor in HIV disease.

oral contraceptives; zidovudine; drug screening /evaluation; pharmacokinetics; drug interactions; oral administration; intravenous administration; gender difference; hormone therapy; medroxyprogesterone; clinical research; human subject;

Vertical transmission of HIV-1 from infected mothers to their newborn infants occurs most frquently during the time of delivery. Treatment of mothers during pregnancy, and labor and delivery, as well as post birth treatment of the infant with zidovudine has reduced the risk of transmission of HIV-1 to the newborn from 25% to 8%. The addition of a single dose of a potent long acting antiretroviral agent such as nevirapine administered to the mother during labor and the infant shortly after birth may potentially further decrease the risk of neonatal aquisition of HIV. The purpose of this study is to evaluate the effect of a single dose of nevirapine given to a mother during labor, in conjuction with a single dose of nevirapine given to the newborn, on the transmission of HIV-1 from infected mothers to their infants.

Proposal Title: RUI: Mechanisms regulating facultative migrations of the Pine Siskin
Institutions: Loyola Marymount University, and a partnership with UC-Davis
Abstract Date: 03/13/2015

Migratory behavior can be characterized by regular and predictable seasonal and directional movements, or the movements may be much less predictable with respect to both timing and direction. The less predictable movements, known as facultative migration, are much more difficult to study. This project will investigate the drivers of facultative migration in a captive species of bird, the pine siskin (Spinus pinus). The goals of the project are to assess 1) What cue(s) trigger the development of a migratory stage; and 2) What endocrine hormones mediate the migratory response? Four cues (photoperiod, food availability, population density, and mate availability) and two hormones (corticosterone and testosterone) will be investigated. Understanding how animals respond to environmental variability is critical in today's changing climate. The project will train a post-graduate researcher at a primarily undergraduate institution, and will involve large numbers of undergraduates, including those from underrepresented groups. The lead investigator is a beginning investigator.

The project will systematically and comprehensively investigate the mechanisms underlying facultative migration, a suite of behaviors that are taxonomically widespread. It is the captive avian model organism that enables this research. Four different hypotheses will be investigated as part of the first goal of the project: (i) an increasing photoperiod stimulates facultative migration in the spring; (ii) declining food availability stimulates the development
of migration; (iii) high local population density, prior to a decline in food availability, can trigger the transition to a migratory
 stage; and (iv) that a shortage of potential mates can stimulate migration around the time of breeding. Two additional hypotheses will be investigated as part of the second goal: (i) increased circulating corticosterone levels stimulate 
the development of a migratory stage; and (ii) the transition to a migratory stage is stimulated
 by increased circulating testosterone levels. Experiments will include manipulating the environmental triggers and tracking behavioral and physiological responses, and direct manipulation of the endocrine hormones. The combined approaches will provide significant opportunities for research training at a primarily undergraduate institution. The team will work with the Loyola Marymount University Center for Urban Resilience to develop and disseminate materials to be used in Los Angeles area schools.