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Virus Found in Lemur Genome May Provide Insights into Human HIV Infections

NEW YORK (GenomeWeb News) – Lentiviruses, viruses related to HIV, may have found their way into primate genomes millions of years ago, according to new research that’s scheduled to appear online this week in the Proceedings of the National Academy of Sciences.
 
By screening sequence data on almost two dozen primate species, a team of researchers from the US and the UK identified a lentivirus called pSIVgml in the genome of Madagascar’s gray mouse lemur (Microcebus murinus). Based on their comparisons between the new virus and other known lentiviruses, the team suggested that such viruses may have entered primate genomes between 14 million and 85 million years ago. And, they say, this long lentiviral-primate history could yield clues about modern lentiviral infections.
 
“The discovery of pSIVgml — the first endogenous primate lentivirus — unequivocally demonstrates that lentiviruses are capable of invading primate genomes,” senior author Robert Schafer, an infectious disease researcher at Stanford University, and his co-workers wrote. “Moreover, it illustrates the utility of endogenous sequences for the study of modern retroviruses, including lentiviruses.”
 
Lentiviruses are a group of complex retroviruses — enveloped, RNA-based viruses — that infect several types of mammals. For instance, HIV-1 is closely related to a group of lentiviruses known to circulate in African apes and monkeys. Non-human primates do not develop AIDS from the simian HIV, though transmission of HIV-1 to humans has caused both pandemic and epidemic outbreaks.
 
But despite the importance of lentiviruses in human health, Schafer and his team noted, “the long-term evolutionary history of lentiviruses, including their origin within primates and the timescale of their interaction with mammals, and the pattern of viral gene acquisition and loss, remain unknown.”
 
Last year, British and American researchers reported finding the first endogenous lentivirus in the genome of a European rabbit.
 
In an effort to find more of these endogenous retroviruses, which integrate into vertebrate germ cells and are then passed on to the next generation, Schafer and his team used the tBLASTn computer program to screen the genomes of 23 primates for additional endogenous lentiviruses. The researchers reasoned that by exploring the “molecular ‘fossil record’” of lentiviruses in primate genomes, they could gain new insights into retroviral history and evolution.
 
In their initial screen, the team discovered that the gray mouse lemur genome contained several peptides matching lentiviruses. When they delved a bit deeper, they found sequences representing 5’ and 3’ lentivirus long terminal repeats as well as viral coding regions such as gag and pol.
 
The researchers dubbed the new endogenous lentivirus the gray mouse lemur prosimian immunodeficiency virus, or pSIVgml. In their subsequent analysis, they found bits and pieces of the virus in at least ten different spots in the genome.
 
Because the available sequence data represented just a third or so of the complete gray mouse lemur genome, the researchers estimated that there are likely six full-length pSIVgml insertions and 24 solo (recombined) LTRs in the animal’s full genome.
 
The virus itself appears to have a typical lentivirus genome structure and a consensus genome sequence of nearly 7,400 nucleotides, including typical lentiviral coding sequences such as gag, pol, and env.
 
When the researchers did phylogenetic analyses, comparing the new virus with known lentiviruses, they found that pSIVgml is basal to simian immunodeficiency viruses and an intermediate viral form between the lentiviruses that infect African primates and those found in non-primates, such as cats.
 
Together with the discovery of an endogenous lentivirus in the European rabbit genome, the new research suggests lentiviruses are older than previously believed. For instance, the researchers estimated that lentiviruses may have associated with ancestral primates between about 14 million and 85 million years ago.
 
Even so, they say, more research is necessary to hone such estimates and better understand the evolution of lentiviruses in primates. The authors noted that by looking in more mammalian genomes, it should be possible to detect additional endogenous lentiviruses that help clarify lentiviral evolution and the history of the viruses’ associations with animals.
 
And because HIV belongs to the lentivirus group, researchers say new insights into the relationship between lentiviruses and primates may provide clues about strategies other organisms use to mount defenses against such retroviruses.
 
“[The research] raises a bunch of interesting questions about how mammals have dealt with these types of viruses over a minimum of 14 million years, and what kind of defenses they have developed, and why some mammal species have lost these types of viruses,” University of Alabama virologist Beatrice Hahn, who was not involved in the study, said in a statement.

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