Herpes STDs: From Chimps to Humans to Cold Sore Cousin Mixing Before Worldwide Spread

It’s an axiom of the infectious disease research community that wherever humans go, germs are likely to follow. Such is the case with the herpes virus family.

There are two main strains, herpes simplex virus 1 and 2 (HSV1 and 2). HSV1 is mostly transmitted by mouth, and seen most often in the common cold sores (affecting two-thirds of the world’s population). HSV-2 is the main culprit of genital herpes (global prevalence of 11 percent), but has even been used to help verify the accepted ancient migrations of humans “Out of Africa” dogma that began about 80,000–50,000 years ago.

Evolutionarily, HSV1 and 2 are considered cousins, and are thought to have evolved independently. Now, an entirely new picture is emerging.

First, research team leader and corresponding author Calvignac-Spencer wanted to build on prior work, which found a new variant of HSV2 isolated only in sub-Saharan African individuals (they explored African populations because they have the highest prevalence of HSV1 and 2 in the world). They wanted to expand their work by analyzing more of these HSV variants and compare their evolutionary divergence to each other.

“We had in mind a paper published by Wertheim et al. (2014) in Molecular Biology and Evolution,” said Calvignac-Spencer. “They showed that HSV2 was likely the result of a very old zoonotic transmission from the chimpanzee/bonobo lineage to the human one. We thought that maybe in these African HSV2 samples, there would be recombinant traces of additional transfers. So we wanted to perform inclusive recombination analyses, using the single chimpanzee alpha herpes virus genome available as well as HSV1 genomes.”

Now, using the whole genome sequencing data of 18 HSV2 isolates, Calvignac-Spencer and colleagues at Berlin’s Robert Koch Institut and Paris’ University Hospital La Pitié-Salpêtrière—Charles Foix have further explored the evolutionary history of the virus.

Although they did not find evidence of chimpanzee herpes virus fragments in HSV2 genomes, they show the history of HSV2 was marked by recombination with HSV1. In addition, they determined two main lineages of HSV2, one globally distributed and another restricted to sub-Saharan Africa, which both started diversifying about 30,000 years ago (kya). The global HSV2 shows evidence of ancient mixing with the HSV1 virus, which through computational tools, they traced back to occurring between 34,000 and 95,000 thousand years ago (kya).

“Our results show that, contrary to common belief, mixed HSV1/HSV2 infections have led to natural gene flow from HSV1 into HSV2 genomes,” said Calvignac-Spencer. “This went unnoticed for a while even though all HSV2 genomes published until our study included recombinant fragments. We were lucky enough that our sampling included the “untouched” African lineage and that our initial objective pushed us to also include HSV1 genomes in recombination analyses.”

“We propose a model of HSV2 evolution in which, following a putative transmission from chimpanzees to the human lineage, HSV2 diversified in African populations before a single lineage characterized by recombinant HSV1 fragments (the worldwide lineage) accompanied the migration of Homo sapiens out of Africa. African HSV2 belonging to the worldwide lineage may be the result of later contacts to non-African populations. Our results also pinpoint that HSV1/HSV2 co-infections occurring today may have some public health relevance.”