Dept. of Microbiology and Immunobiology
Division of Microbiology
Harvard Medical School
One Pine Hill Drive
Southborough, MA 01772
The genomes of all metazoan species are riddled with the remnants of ancient retroviral epidemics in the form of integrated proviruses. These DNA “fossils” are a testament to the great adaptability of the retroviridae and serve as proof that the lineages of all living species have been subject to retroviral onslaughts for tens of millions of years. Although we are generally not aware of it, when we study infection and replication of retroviruses in the lab, we are studying relationships that have been fine-tuned by millions of years of co-evolution of retroviruses and their animal hosts.
In our laboratory, we use a comparative approach to understand the virus-host relationship, focusing on the primate lentiviruses (HIV-1, HIV-2 in humans and the >40 SIV strains found in old world monkeys). Projects typically begin with molecular phylogenetic analyses of viruses or relevant host genes, and often entail sampling both within and between species. These analyses then drive hypotheses and subsequent design of molecular and cellular experiments in the lab. Thus, projects in the laboratory bridge evolutionary biology and traditional, molecular and cellular virology, and trainees (graduate students and postdocs) are likely to develop expertise in both virology and molecular evolution. While this work is relevant to HIV/AIDS in humans, even more broadly, we hope to arrive at a general understanding of how host genetic variation influences patterns of cross-species transmission, adaptation and emergence of viruses.
Ph.D. Tufts University School of Medicine, Boston, MA
Kirmaier, A., Wu, F., Newman, R., Hall, L.R., Morgan, J.S., O’Connor, S., Marx, P.A., Meythaler, M., Goldstein, S., Buckler-White, A., Kaur, A., Hirsch, V., Johnson, W.E.2010. TRIM5 Suppresses Cross-species Transmission of a primate immunodeficiency virus and selects for emergence of resistant variants in the new species. PLoS Biology - In press.
Newman, R.M., Hall, L., Kirmaier, A., Pozzi, L., Pery, E., Farzan, M., O’Neil, S.P., Johnson, W.E. 2008. Evolution of a TRIM5-CypA Splice Isoform in Old World Monkeys. PLoS Pathogens 4(2):e1000003.
Newman, R.M., Hall, L.R., Connole, M., Chen, G-L, Yuste, E., Diehl, W., Hunter, E., Kaur, A., Miller, G., Johnson, W.E.2006. Balancing Selection and Functional Polymorphism in Old World Monkey TRIM5a. Proceedings of the National Academy of Sciences 103(50)19134-19139.
Sato, S., Yuste, E., Lauer, W.A., Chang, E-H., Morgan, J.S., Bixby, J.G., Lifson, J.D., Desrosiers, R.C., and Johnson, W.E. 2008. Potent antibody mediated neutralization and evolution of antigenic escape variants of simian immunodeficiency virus strain SIVmac239 in vivo. Journal of Virology 82:9739-52. PMID: 18667507.
Johnson, W.E. 2008. A Proviral Puzzle with a Prosimian Twist. Proceedings of the National Academy of Sciences 105:20051-20052.
Johnson, W.E. and Sawyer, S.L. 2009. Evolution of the antiretroviral TRIM5 gene. Immunogenetics 61:63-76. PMID: 19238338.