Discovery of Novel Herpes Simplexviruses in Wild Gorillas, Bonobos, and Chimpanzees Supports Zoonotic Origin of HSV-2

Wertheim, Joel O.; Hostager, Reilly; Ryu, Diane; Merkel, Kevin; Angedakin, Samuel; Arandjelovic, Mimi; Ayimisin, Emmanuel Ayuk; Babweteera, Fred; Bessone, Mattia; Brun-Jeffery, Kathryn J.; Dieguez, Paula; Eckardt, Winnie; Fruth, Barbara; Herbinger, Ilka; Jones, Sorrel; Kuehl, Hjalmar; Langergraber, Kevin E.; Lee, Kevin; Madinda, Nadege F.; Metzger, Sonja; Ormsby, Lucy Jayne; Robbins, Martha M.; Sommer, Volker; Stoinski, Tara; Wessling, Erin G.; Wittig, Roman M.; Yuh, Yisa Ginath; Leendertz, Fabian H.; Calvignac-Spencer, Sébastien

Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.