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

Abstract

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 co-divergence 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 million years, the most recent of which occurred between humans and bonobos around 1 million years ago. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.

Phylogeographic analysis reveals an ancient East African origin of the human herpes simplexvirus 2 dispersal out-of-Africa

“…5), post-dating the original human out-of-Africa migratory event by tens of thousands of years (10). The rates that infer these migration dates also infer date of initial divergence in HSV-2 consistent with previous TMRCA estimates for HSV-2 between 90-120 kya (7, 8). It is therefore unlikely that current worldwide HSV-2 diversity is the result of migrating with modern humans during the original out-of-Africa migration between 50 and 100 kya, as this scenario would place the TMRCA of HSV-2 between 250 and 500 kya, predating modern humans as well as previous HSV-2 age estimates.…”

“…Purple boxes indicate ages and events with respect to out-of-Africa dispersal. (7) Timing of first human migrations out of Africa estimated to be 50-100 kya (10). (8) Timing of trans-Atlantic slave trade ca.…”

“…In 2016, worldwide the prevalence of HSV-2 was 13%; the highest prevalence is in Africa with around 44% of female population and 25% of male population living with HSV-2 (4). HSV-2 has ancient zoonotic origins, whereby proto-humans in Africa were infected by an ape simplexvirus (5)(6)(7).…”

“…For HSV-2, there is no detectable relationship between the year of viral sampling and the distance from the root of the phylogeny (11, 15). The hypothesis of human migration out-of-Africa as a mechanism for HSV-2 dispersal arises from molecular clock estimates calibrated based on inference of codivergence events deeper in the simplexvirus tree that suggest a genome-wide clock rate on the order of 10 −8 substitutions/site/year (5, 7, 8, 16). In contrast, the hypothesis that the trans-Atlantic slave trade was the route for HSV-2 worldwide dispersal is based upon a power-law rate decay of the molecular clock, whereby more recent branches have a faster clock rate than older branches (17), with an intercept of 3.3×10 − 3 substitutions/site/year (11).…”

Homo medicus: The transition to meat eating, increased pathogen pressure, and the constitutive and inducible use of pharmacological plants in Homo

“…Herpes simplex virus 1 (HSV-1), which infects over two thirds of the human population, mainly by an oral route, appears to have codiverged with the the human lineage after it diverged from one of the other great apes, probably gorillas (Wertheim et al, 2021). HSV-2, on the other hand, which causes most cases of genital herpes and infects about 11% of the population, appears to have spilled over from bonobos into the human lineage around 1 mya, after bonobos diverged from chimpanzees c. 2.1 mya (Wertheim et al, 2021). This overlaps the time frame of the transition to greater meat eating.…”