title: Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract.
abstract: Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium. DOI:http://dx.doi.org/10.7554/eLife.00288.001.
authors.affiliation: Vaccine and Infectious Diseases Division , Fred Hutchinson Cancer Research Center , Seattle , United States ; Department of Medicine , University of Washington , Seattle , United States.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Schiffer
authors.forename: David
authors.initials: D
authors.lastname: Swan
authors.forename: Ramzi
authors.initials: R
authors.lastname: Al Sallaq
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.forename: Karen E
authors.initials: KE
authors.lastname: Mark
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.forename: Negusse
authors.initials: N
authors.lastname: Ocbamichael
authors.forename: Steve
authors.initials: S
authors.lastname: Kuntz
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.forename: Barry
authors.initials: B
authors.lastname: Robinson
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D003198:Computer Simulation; D004279:DNA, Viral / Q000096:biosynthesis*; D005835:Genitalia / Q000276:immunology / Q000821:virology*; D006558:Herpes Genitalis / Q000276:immunology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007700:Kinetics; D018448:Models, Immunological; D019562:Viral Load; D014775:Virus Activation; D017201:Virus Shedding
chemical_list: D004279:DNA, Viral
keywords: Herpes simplex; Human; Mathematical modeling; Mucosal immunity; Other; Viruses