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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI030731-27
Application #
9307675
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
27
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Schiffer, Joshua T; Swan, Dave A; Roychoudhury, Pavitra et al. (2018) A Fixed Spatial Structure of CD8+ T Cells in Tissue during Chronic HSV-2 Infection. J Immunol 201:1522-1535
Traidl, Stephan; Kienlin, Petra; Begemann, Gabriele et al. (2018) Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus-specific type 2 immune responses. J Allergy Clin Immunol 141:1144-1147.e5
Ramchandani, Meena; Selke, Stacy; Magaret, Amalia et al. (2018) Prospective cohort study showing persistent HSV-2 shedding in women with genital herpes 2 years after acquisition. Sex Transm Infect 94:568-570
Boucoiran, Isabelle; Mayer, Bryan T; Krantz, Elizabeth M et al. (2018) Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants. Pediatr Infect Dis J 37:627-631
Kleinstein, Sarah E; Shea, Patrick R; Allen, Andrew S et al. (2018) Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2). Genes Immun :
Abana, Chike O; Pilkinton, Mark A; Gaudieri, Silvana et al. (2017) Cytomegalovirus (CMV) Epitope-Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects. J Immunol 199:3187-3201
Johnston, Christine; Magaret, Amalia; Roychoudhury, Pavitra et al. (2017) Highly conserved intragenic HSV-2 sequences: Results from next-generation sequencing of HSV-2 UL and US regions from genital swabs collected from 3 continents. Virology 510:90-98
Agyemang, Elfriede; Le, Quynh-An; Warren, Terri et al. (2017) Performance of Commercial Enzyme-Linked Immunoassays for Diagnosis of Herpes Simplex Virus-1 and Herpes Simplex Virus-2 Infection in a Clinical Setting. Sex Transm Dis 44:763-767
Stankiewicz Karita, Helen C; Moss, Nicholas J; Laschansky, Ellen et al. (2017) Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy. Open Forum Infect Dis 4:ofx248
Looker, Katharine J; Magaret, Amalia S; May, Margaret T et al. (2017) First estimates of the global and regional incidence of neonatal herpes infection. Lancet Glob Health 5:e300-e309

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