Herpes simplex virus type 1 (HSV-1) has emerged as the leading cause of both genital herpes in young adults and neonatal herpes. Despite the increasing importance of genital HSV-1, the natural history of genital HSV-1 has not been characterized. We lack knowledge regarding: 1) frequency of viral shedding after primary infection by anatomic site;2) persistence of genital inflammatory response to HSV-1 and its potential to increase the risk of HIV acquisition;and 3) risk factors for HSV-1 transmission, including oral and genital viral shedding patterns in the transmitting partner. To address these gaps, we propose:
Aim 1. Define the natural history of oral and genital HSV-1 shedding during the first year of infection. We hypothesize that genital shedding rates will decrease dramatically during the first year after infection, possibly indicating development of a successful immune response to HSV-1. We will enroll 100 persons with laboratory documented primary genital HSV-1 infection to measure genital and oral HSV-1 shedding at 2 and 11 months post infection, through 30-day oral and genital self-swabbing studies.
Aim 2. Determine whether HSV-1 acquisition and genital shedding are associated with infiltrates of HIV-receptor bearing CD4 T cells, dendritic cells and CDS T cells in the genital tract. We hypothesize that CD4 and CDS T cells will persist at the site of the primary genital lesions for months, and the magnitude of inflammation will be positively associated with genital shedding rate. 50 participants will have frequent blood draws and genital biopsies at the end of each shedding session to assess the persistence of genital tract inflammation, as measured by concentration of CD4 and CDS T cells.
Aim 3. Determine whether transmitting partners have HSV-1 infection at the oral or genital site, or both. We will enroll 50 persons who transmitted HSV-1 to their partners genital area to collect oral and genital swabs and determine whether a high rate of shedding at either site is associated with a shorter time to HSV-1 transmission to susceptible partner. Together, these studies will help us understand transmission dynamics of genital HSV-1 infection and will provide insight into the genital immune response to HSV-1 to inform HSV vaccine design
Herpes simplex virus type 1 (HSV-1) is an increasing cause of genital and neonatal herpes;however, we lack knowledge about clinical aspects of genital HSV-1 infection. This study will enroll persons with primary genital-HSV-I and their partners to define risk factors for transmission, and associations between oral and genital shedding, the development of the immune response, and genital inflammation.
|Posavad, C M; Zhao, L; Mueller, D E et al. (2015) Persistence of mucosal T-cell responses to herpes simplex virus type 2 in the female genital tract. Mucosal Immunol 8:115-26|
|Melvin, Ann J; Mohan, Kathleen M; Schiffer, Joshua T et al. (2015) Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection. J Pediatr 166:827-33|
|Perti, Tara; Nyati, Mandisa; Gray, Glenda et al. (2014) Frequent genital HSV-2 shedding among women during labor in Soweto, South Africa. Infect Dis Obstet Gynecol 2014:258291|
|Dhankani, Varsha; Kutz, J Nathan; Schiffer, Joshua T (2014) Herpes simplex virus-2 genital tract shedding is not predictable over months or years in infected persons. PLoS Comput Biol 10:e1003922|
|Gantt, Soren; Cattamanchi, Ashok; Krantz, Elizabeth et al. (2014) Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy. J Clin Virol 60:127-32|
|Johnston, Christine; Zhu, Jia; Jing, Lichen et al. (2014) Virologic and immunologic evidence of multifocal genital herpes simplex virus 2 infection. J Virol 88:4921-31|
|Slyker, Jennifer; Farquhar, Carey; Atkinson, Claire et al. (2014) Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection. Clin Infect Dis 58:564-72|
|Delaney, Shani; Gardella, Carolyn; Saracino, Misty et al. (2014) Seroprevalence of herpes simplex virus type 1 and 2 among pregnant women, 1989-2010. JAMA 312:746-8|
|Phipps, Warren; Saracino, Misty; Selke, Stacy et al. (2014) Oral HHV-8 replication among women in Mombasa, Kenya. J Med Virol 86:1759-65|
|Mark, Karen E; Spruance, Spotswood; Kinghorn, George R et al. (2014) Three phase III randomized controlled trials of topical resiquimod 0.01-percent gel to reduce anogenital herpes recurrences. Antimicrob Agents Chemother 58:5016-23|
Showing the most recent 10 out of 270 publications