Researchers find that disease-causing viruses puts pressure on primates to co-evolve with the virus to increase chances of survival.
Lentiviruses are pathogenic viruses that delay the presence of symptoms after initial infection. They have been proposed to be endemic to African primates for many generations, such as HIV that affects humans and the simian immunodeficiency virus (SIVs) that affects Old World monkeys and apes; HIV is derived from SIVs based on a common carrier.
Mortality rates and their associated clinical symptoms of humans infected with HIV have been typically observed to be high, while, interestingly, primates that have been hosts of SIV are less likely to demonstrate such overt outcomes. Given the that hosts of SIV are capable of non-pathogenic infection, it would not be a stretch to infer that the hosts and the virus co-evolved throughout history for this to occur.
The TRIM5 protein is a restriction factor, meaning that its expression is able to block retroviral infection by binding to the (lenti)virus. Any evolutionary changes to TRIM5 in species over time would indicate any adaptations that were made in order to protect the species from viral infection.
Researcher Welkin Johnson and colleagues studied the adaptive mutations of TRIM5 by isolating its variant from 22 African primate species and comparing it to TRIM5. A corollary goal to constructing an evolutionary tree of TRIM5 would be to expose the TRIM5 genes to various lentiviruses and observe the response.
The research team was able to confirm that adaptive mutations unique to the TRIM5 proteins of Cercopithecinae, a subset of African monkeys that includes macaques and baboons. Moreover, the findings suggest that ancestral lentiviruses similar to modern SIVs began to infect primates in Africa as far as 16 million years ago.
While the research team was only able to determine the correlation that adaptations of TRIM5 were restricted to the same hosts, they remarkably shed light on how evolution of gene specificity occurs over millennia under positive selection. That is, advantageous mutations in the TRIM5 gene which mediates contact between the virus’ protein shell and the host in favour of host survival. These advantageous mutations, by effect of positive selection, increases the frequency of the beneficial alleles in the population. In light of the evidence, the researchers were unable to account for the factor that could account for positive selection.
The findings were strengthened by the fact that adaptations in TRIM5 amongst Cercopithecinae occurred in two independent lineages, which in effect posit that an overlapping target (of the virus) was recognized by TRIM5.
What does this mean for the most common lentivirus that affects humans?
While the TRIM5 gene is present in humans, it either has not (yet) undergone the selective pressure to mutate to resist HIV or the virus is able to evade it.
However, individuals from Nordic countries are much more likely to be resistant or immune to HIV infection by blocking its entry into cells. Researchers are in disagreement between whether smallpox or the bubonic plague (Black Death) exerted selective pressure on the frequency of the mutated gene, known as CCRA-delta32 that confers the advantage.
On one hand, smallpox has been present for approximately 2,000 years in Europe, particularly in areas where milking of cows was abundant—likely because of higher altitudes and consequent lack of vitamin D access. The biological similarities of smallpox and HIV are close, as both are viruses, and individuals surviving smallpox were naturally selected to pass on the mutation for generations (and in effect surviving Black Death). Withstanding this remains the question of why the smallpox virus was a selective event in HIV resistance.
Positive selection influenced the evolution of TRIM5 against SIV in Cercopithecinae species similar to CCRA-delata32 against HIV in humans. The methods, findings and their meanings can be extrapolated to further the studying of inheritable genes and how they may co-evolve in the survival of a species.