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.
|Magaret, Amalia S; Mujugira, Andrew; Hughes, James P et al. (2016) Effect of Condom Use on Per-act HSV-2 Transmission Risk in HIV-1, HSV-2-discordant Couples. Clin Infect Dis 62:456-61|
|Oseso, Linda; Magaret, Amalia S; Jerome, Keith R et al. (2016) Attitudes and Willingness to Assume Risk of Experimental Therapy to Eradicate Genital Herpes Simplex Virus Infection. Sex Transm Dis 43:566-71|
|Magaret, A; Dong, L; John, M et al. (2016) HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions. Genes Immun 17:412-418|
|Jing, Lichen; Laing, Kerry J; Dong, Lichun et al. (2016) Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses. J Immunol 196:2205-18|
|Manguro, Griffins O; Masese, Linnet N; Deya, Ruth W et al. (2016) Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy. PLoS One 11:e0163541|
|Ramchandani, Meena; Kong, Marlene; Tronstein, Elizabeth et al. (2016) Herpes Simplex Virus Type 1 Shedding in Tears and Nasal and Oral Mucosa of Healthy Adults. Sex Transm Dis 43:756-760|
|Milman, Neta; Zhu, Jia; Johnston, Christine et al. (2016) In Situ Detection of Regulatory T Cells in Human Genital Herpes Simplex Virus Type 2 (HSV-2) Reactivation and Their Influence on Spontaneous HSV-2 Reactivation. J Infect Dis 214:23-31|
|Tjernlund, Annelie; Burgener, Adam; Lindvall, Jessica M et al. (2016) In Situ Staining and Laser Capture Microdissection of Lymph Node Residing SIV Gag-Specific CD8+ T cells--A Tool to Interrogate a Functional Immune Response Ex Vivo. PLoS One 11:e0149907|
|Nason, Martha C; Patel, Eshan U; Kirkpatrick, Allison R et al. (2016) Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment. Open Forum Infect Dis 3:ofw073|
|Bender Ignacio, Rachel A; Goldman, Jason D; Magaret, Amalia S et al. (2016) Patterns of human herpesvirus-8 oral shedding among diverse cohorts of human herpesvirus-8 seropositive persons. Infect Agent Cancer 11:7|
Showing the most recent 10 out of 311 publications