Nonhuman Primate Transcriptome Project Makes Progress

This year’s 29th Annual Symposium on Nonhuman Primate (NHP) Models for AIDS, which takes place from October 25-28 in Seattle, has about 50% more registrants than last year, and the number of international registrants has doubled, said David Anderson, conference chair and director of the Washington National Primate Research Center. It could be the beautiful location, but Anderson said part of the reason is that NHP research is becoming more collaborative. “I think part of why we have an increase in attendance this year is because science is getting bigger, more complex and getting characterized by partnerships,” he said, adding that one example is systems biology which involves “pulling people from a lot of different areas together.”

Another example of how the field is currently moving towards large scale projects is the NHP reference transcriptome project, which aims to sequence the transcriptomes (the totality of all expressed RNAs) of no less than 20 tissues from 15 NHP species.

Michael Katze, co-host of today’s session on virus-host interactions and genomics and a member of the project’s steering committee, said that the company Illumina has been doing the sequencing for the project for free, and that just 18 months after the project was launched, the transcriptomes of five species are done. “Five out of 15 [species]—all in 18 months, it’s really phenomenal,” said Katze, who is also associate director at the Washington National Primate Research Center.

The transcriptome, Katze said, will enable researchers to improve the annotation of the genome sequences of some of these species. “The rhesus genome was built with 2006 technology,” he said. “We are five years later, and now you inform the genome by looking at RNA expression, which is really probably the biggest deal.” Knowing the transcriptome may also result in the identification of novel restriction factors that affect how easy it is to infect animals with challenge viruses, Katze said.

It’s also important to characterize the known restriction factors in NHPs, to be able to avoid variations in the outcome of challenge experiments. For example, restriction factors such as TRIM5 can restrict SIV replication and therefore affect the outcome of challenge experiments. To address this in cynomolgus macaques (Macaca fascicularis), Elizabeth Dietrich of the University of Washington studied how different versions of the restriction factor TRIMCyp (taken from cynomolgus macaques from different geographical areas) can affect the susceptibility of cultured cells to infection with HIV-1 and HIV-2.

She found specific amino acid changes in TRIMCyp that can alter the susceptibility to these viruses. This suggests that changes in these amino acids might also affect the susceptibility to infection with SIV challenge viruses. Eventually, Dietrich said, it should be possible to use this knowledge to check if animals to be used in challenge studies don’t express a version of TRIMCyp that changes the outcome of challenge experiments.