Primate immune genetics and genomics

Macaque monkeys are widely used in biomedical research. They also develop AIDS after infection with simian immunodeficiency virus (SIV), a virus that is nearly identical to HIV. Macaques are therefore the best animals for testing novel AIDS vaccine concepts and understanding AIDS pathogenesis. The severity of SIV infection varies among macaques, likely owing to genetic differences. A major research emphasis in our lab is understanding how macaque genetics influence susceptibility and resistance to infectious diseases, specifically SIV. We are particularly interested in the major histocompatibility complex (MHC), a cluster of genes that bind and present peptides to T cells. We are also characterizing variation in other macaque immune gene families, such as the killer immunoglobulin receptors and FC gamma receptors.

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Primate genomics

It is now possible to sequence entire primate genomes for less than $5,000 and exomes for less than $1,000. We partnered with the Human Genome Sequencing Center at Baylor College of Medicine to sequence genomes and exams from macaques. We have now examined hundreds of genomes and exomes from rhesus and cynomolgus macaques. Though this data is not published yet, it can be freely accessed here. We are working to develop tools and strategies for "personalized medicine" in macaques, since we envision a time in the near-future where full genome analysis will be a routine component of all macaque research studies.

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Zika virus association with fetal abnormalities

Zika virus can cause microcephaly and other fetal abnormalities. We have developed a rhesus macaque model for studying Zika virus during pregnancy. The goal of this model is to define when during pregnancy a woman is at greatest risk of adverse fetal outcomes and test interventions that could prevent or reverse these outcomes.

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HIV pathogenesis

Globally, there are more than 30 million individuals living with HIV/AIDS, a number that is growing by approximately 2 million each year. An overarching goal of my laboratory is to contribute meaningfully to the global response to HIV. Though HIV is a preventable and treatable disease, the sheer number of new HIV infections demonstrates that a prophylactic vaccine is desperately needed to augment existing prevention programs. Most vaccine concepts are prototyped in macaques infected with simian immunodeficiency virus (SIV). Therefore, our laboratory studies both SIV-infected macaques and HIV-infected people. A short essay describing my philosophy towards nonhuman primate experimentation is available here.

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  • Expansion of Simian Immunodeficiency Virus (SIV)-Specific CD8 T Cell Lines from SIV-Naive Mauritian Cynomolgus Macaques for Adoptive Transfer. J Virol 89:9748. PMC4577914
  • Whole-genome characterization of human and simian immunodeficiency virus intrahost diversity by ultradeep pyrosequencing. J Virol 84(22):12087-12092. PMC2977871.
  • Cross-clade simultaneous HIV drug resistance genotyping for reverse transcriptase, protease, and integrase inhibitor mutations by Illumina MiSeq. Retrovirology 11:122. PMC4302432

Discovery of novel viruses

We have discovered many RNA viruses in nonhuman primates and are using macaques to understand how these viruses impact human health. Some of these impacts may be beneficial; ror example, people infected with both GBV-C and HIV exhibit slower progression to AIDS (we also described a similar effect in the recent West African Ebola outbreak). We will use the monkey GBV-C viruses to try and recapitulate this effect in SIV+ monkeys with the goal of understanding how GBV-C mitigates the severity of immunodeficiency virus infection. We are also assessing whether any of the viruses we have discovered pose an unappreciated threat of causing disease in humans.

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