Mike, Adam, and Trent analyzing macaque genome data.

Dawn generating HIV drug resistance genotypes.

Christina looking at genetically modified mosquitoes designed to fight Zika virus.

The overarching goal of the O’Connor lab is to contribute meaningfully to the global response to viral infections impacting human health. We do this by studying the interplay of viral pathogenesis, host genomics, and immunity. The lab currently has six major research areas (described below) with most of our research support coming from the National Institutes of Health.

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In close collaboration with Dr. Tom Friedrich, we lead the CoVen, an international collaboration of investigators developing COVID-19 nonhuman primate models to test vaccines and medical countermeasures. Closer to home, Tom and my group have been responsible for sequencing SARS-CoV-2 genomes from cases throughout Dane and Milwaukee Counties to understand how these viruses are moving through Wisconsin. We are also working with Dave Beebe, a biomedical engineer, to develop scalable, SARS-CoV-2 nucleic acid testing that can be used to screen institutions like nursing homes and large workplaces. Information on our COVID-19 research including real-time data can be found at http://openresearch.labkey.com.

HIV pathogenesis

Globally, there are more than 35 million individuals living with HIV/AIDS, a number that is growing by approximately 1.8 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.

For more information:

  • Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication. PLoS Pathog. PMC5142784.
  • 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

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.

For more information:

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.

For more information:

Primate genomics

It is now possible to sequence entire primate genomes for approximately $1,000 and exomes for less than $500. 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. 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.

For more information:

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, with a particular emphasis on simian arteriviruses. While these viruses have not, to our knowledge, infected humans, they share worrisome similarities in their natural primate hosts with the simian immunodeficiency viruses that gave rise to the HIV epidemic.

For more information:

  • Zoonotic Potential of Simian Arteriviruses. J Virol 90:630. PMC4702702
  • Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses. J Virol.  PMC4505640
  • GB Virus C Coinfections in West African Ebola Patients. J Virol. PMC4338908–.
  • Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection. Sci Transl Med. PMC4605385
  • Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection. PLoS Pathog. PMC5675458.
  • The Coming Plague: Newly Emerging Diseases in a World Out of Balance