Herpes Simplex Virus Study Confirms ‘out of Africa’ Migration of Ancient Humans

Herpes Simplex virus HSV-1 confirms out of Africa migration in humans
Researchers from the University of Wisconson-Madison have used the herpes simplex virus 1 genome to tentatively confirm the “out of Africa” migration theory in humans, and could even hint at genetic virulence

A comprehensive study of a remarkably common virus, called herpes simplex virus 1 (HSV-1), is reported to confirm the “out of Africa” pattern of migration in human beings. The research could also provide scientists more knowledge on the virulence of particular strains of HSV-1 and influenza. Generally, the theory that humans originated from Africa is a widely accepted posit within the scientific community, based upon genetic studies and fossil records.

The Herpes Simplex Virus

Researchers from the University of Wisconsin-Madison performed an investigation of the full genetic code of 31 strains of the HSV-1 virus, collected from different parts of the globe, and analyzed their genomes using genetic sequencing and intricate bioinformatics tools.

Herpes simplex virus 1 is capable of triggering cold sores, manifesting as mucocutaneous lesions and keratitis within infected human hosts. The virus is both highly contagious and ubiquitous, enduring within the nerve cells of the body after primary infection. Some individuals experience repeated bouts of outbreak, after the virus reactivates and travels along axons of nerves to the skin.

The infectivity of HSV-1 is dependent upon multiple factors, predominately the specific viral strain and the host’s immune system. The researchers claim the HSV-1 genome to be akin to an “external genome” and, due to its ease of collection, lack of lethality and ability to cause sustained latent infections, was an ideal candidate for study.

HSV-1 Strains are Clustered Based Upon Geographical Location

Previous studies have mainly focused upon viral strains of HSV-1 from North America and Europe, with limited phylogenetic studies having been executed, using only single genes or small clusters of genes. The research group maintains these prior studies to be limited and “misleading,” with relationships determined from a single gene, or small sets of genes, proving inaccurate.

During the latest study, which was published in the online journal PLoS One, the researchers used more comprehensive genomic sequences from Eastern Africa, East Asia, Europe and North America to explore the evolutionary relationships between the 31 different strains of HSV-1.

The study identified six different clades, representing a group of descendents of a common ancestor. These six HSV-1 clades were placed into phylogenetic trees to describe their geographical origins. According to Curtis Brandt, a professor of medical microbiology and ophthalmology and senior author of the research study, the results were quite “stunning.” He goes on to describe their preliminary findings:

“The viral strains sort exactly as you would predict based on sequencing of human genomes. We found that all of the African isolates cluster together, all the virus from the Far East, Korea, Japan, China clustered together, all the viruses in Europe and America, with one exception, clustered together.”

HSV1 genome strains put into phylogenetic tree showing relation
Diagram showing the phylogenetic tree for the 31 HSV-1 strains and their six clades. The colors indicate where each strain was derived (light blue: U.S.A., dark blue: U.K., red: China, purple: South Korea, orange: Japan, green: Kenya). Credit: Brandt et al., (2013).

Geneticists are able to determine how organisms are genetically related by exploring alterations in the DNA sequence of their genes. How rapidly an organism’s genome changes then enables researchers to compile a family tree to draw relationships between variants and their common ancestor.

Based upon the “maximum likelihood” phylogenetic tree, generated by Brandt and colleagues, the following HSV-1 clades were witnessed:

  • Clade I: European/North American strains
  • Clade II: East Asian strains
  • Clade III, IV, V and VI: East African

The researchers concluded that six clades of HSV-1 strictly corresponded with their geographic origins, supporting the hypothesis that HSV-1 co-evolved with their human hosts; crucially, this provides additional support to the “out-of-Africa” theory of human evolution.

The four clades of HSV-1 found in Kenyan samples reveals the high level of diversity around this region and, according to the research journal, “… correlates with the genetic diversity of human populations in East Africa.” They elaborate on this finding, speculating that these four clades of HSV-1 could result from the four largest ethnic groups that historically inhabited this region of East Africa, as outlined:

  • Clade III: Bantu Peoples
  • Clade IV: Nilotic peoples
  • Clade V: Cushitic people
  • Clade VI: hunter gatherers
HSV1 genome phylogenetics used to track past human migrations
Map showing the geographic locations of the six clades of HSV-1, which traveled and diversified with their human hosts.

The group produced a world map that showed the geographical location of each of the six HSV-1 clades, relative to proposed human migration patterns. Land migration routes are highlighted by yellow lines, whereas air and seas routes are denoted by pink lines.

It is suggested that small populations began migrating out of Africa, heading towards the Middle East, before reaching an initial bottleneck. These ancient groups then spread towards the Americas, Asia and Europe.

However, the only strain that failed to stack up with this geographical topology pattern was KOS. The KOS viral strain sorts into clade II (East Asian origin), but was actually found in North America. In fathoming why this was the case, the group suggests that it could be the result of a recent global transfer that relates to travel. It is plausible the strain was derived from individuals who had traveled across the Bering Strait land bridge, around 15,000 years ago.

Understanding Other Viruses

Another possible application of the researchers’ study could extend to comparing the entire genomic sequences of other related viral strains. The technology implemented was able to simultaneously compare different viral strains, and could be used to understand why particular variants demonstrate so much more lethality than others.

For example, in a small strain of HSV-1, some infections can cause deadly brain infections, a condition known as herpes simplex encephalitis (HSE). The pathology affects around 1 in half a million people every year, with the virus believed to spread from the face, along nerve axons, into the brain. Those infected with this form of the disease often die, even when treated with intravenous antiviral drugs; survivors, meanwhile, are often left with permanent neurological damage.

Brandt ruminated over these points in a recent press release:

“We’d like to understand why these few viruses are so dangerous, when the predominant course of herpes is so mild. We believe that a difference in the gene sequence is determining the outcome, and we are interested in sorting this out.”

Therefore, it seems, not only do herpes simplex virus 1 strains appear to confirm the “out of Africa” theory of migration, but they might also be used to gain an enhanced understanding of the virulence of many common viruses. Excitingly, the researchers hint that their study methods could even help find genetic-based virulence markers for both herpes simplex and influenza.

By: James Fenner

PLoS Journal Source

Press Release Link

NCBI Information Link

Trends in Ecology and Evolution Journal

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