title: Worldwide circulation of HSV-2 × HSV-1 recombinant strains.
abstract: Homo sapiens harbor two distinct, medically significant species of simplexviruses, herpes simplex virus (HSV)-1 and HSV-2, with estimated divergence 6-8 million years ago (MYA). Unexpectedly, we found that circulating HSV-2 strains can contain HSV-1 DNA segments in three distinct genes. Using over 150 genital swabs from North and South America and Africa, we detected recombinants worldwide. Common, widely distributed gene UL39 genotypes are parsimoniously explained by an initial >457 basepair (bp) HSV-1 × HSV-2 crossover followed by back-recombination to HSV-2. Blocks of >244 and >539 bp of HSV-1 DNA within genes UL29 and UL30, respectively, have reached near fixation, with a minority of strains retaining sequences we posit as ancestral HSV-2. Our data add to previous in vitro and animal work, implying that in vivo cellular co-infection with HSV-1 and HSV-2 yields viable interspecies recombinants in the natural human host.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.|Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.|Department of Global Health, University of Washington, Seattle, WA 98195, USA.|Benaroya Research Institute, Seattle, WA 98102, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.affiliation: Department of Infectious Diseases, University of Gothenburg, Guldhedsgatan 10B, 41346, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Norberg
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fitzgibbon
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ronnie M
authors.initials: RM
authors.lastname: Russell
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Alex L
authors.initials: AL
authors.lastname: Greninger
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Stensland
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Lichen
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.|Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Amalia S
authors.initials: AS
authors.lastname: Magaret
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Diem
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.|Department of Global Health, University of Washington, Seattle, WA 98195, USA.|Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.|Department of Global Health, University of Washington, Seattle, WA 98195, USA.|Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.|Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.|Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.|Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
mesh_terms: D000349:Africa / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006561:Herpes Simplex / Q000453:epidemiology / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009656:North America / Q000453:epidemiology; D010802:Phylogeny; D011995:Recombination, Genetic; D013020:South America / Q000453:epidemiology