Virology Faculty Member - R. Paul Johnson

R. Paul Johnson

Professor of Medicine

New England Regional Primate Research Center
P.O. Box 9102
1 Pine Hill Drive
Southborough, MA 01772-9102
Tel: 508-624-8148
Fax: 508-624-8172
Email: paul_johnson@hms.harvard.edu
Lab Members: 3 postdoctoral fellows, 1 graduate student



The major focus of my laboratory is AIDS-related research, including examination of mechanisms of protective immunity induced by SIV vaccines, analysis of AIDS immunopathogenesis, and characterization of the role of natural killer (NK) cell responses in viral infections. Current projects in my laboratory include:

Immune responses responsible for protection of macaques immunized with live attenuated SIV vaccines. Analysis of protective immunity in macaques immunized with live attenuated SIV strains, one of the most effective vaccine approaches in primates, represents one of the leading experimental models in which to study protective immunity against primate lentiviruses. Prior publications from our laboratory have demonstrated that live attenuated SIV vaccines are able to induce vigorous and durable cellular immune responses and to protect against mucosal challenge. Ongoing research is focused on the use of in vivo lymphocyte depletion studies, as well as the application of multicolor flow cytometric techniques and cDNA microarrays to provide new insights into adaptive and innate immune responses induced by live attenuated SIV strains.

Modulation of PD-1 expression on virus-specific T cells. Chronic viral infections are typically associated with T cell dysfunction, resulting in impaired antiviral effector mechanisms, and ultimately facilitating the ability of the virus to persist in the host. The coinhibitory TCR receptor PD-1 has been proposed to be a specific marker for exhausted or dysfunctional T cells, but recent work from our group and others have shown that PD-1 is also expressed on activated but not dysfunctional T cells. Current work is focused on strategies to more precise identify dysfunctional PD-1+ T cells and to characterize the functional properties of PD-1+ memory T cells.

The role of NK cell responses in SIV infection. NK cells contribute to control of HIV/SIV infection both by lysis of virus-infected cells and cytokine-mediated virus suppression. Recent publications from our laboratory demonstrate that SIV infection induces changes in NK cell function characterized by decreased cytokine production, expanded cytotoxicity, and trafficking away from secondary lymphoid organs to gut-associated lymphoid tissue. Ongoing studies are analyzing the effect of SIV infection on NK cells in gut-associated lymphoid tissues and developing new approaches for the analysis of gene expression in mucosal NK cells.



Last Update: 10/22/2013



Publications

Gauduin M-C, Yu Y, Barabasz A, Carville A, Piatak M, Lifson JD, Desrosiers RC, Johnson RP. Induction of a virus-specific effector memory CD4+ T cell response by attenuated SIV infection. J. Exp. Med. 2006; 203:2661-2672.

Salisch NC, Kaufmann DE, Awad AS, Reeves RK, Tighe D, Li Y, Piatak M, Lifson JD, Evans DT, Pereyra F, Freeman GJ, Johnson RP. The inhibitory TCR co-receptor PD-1 is a sensitive indicator of low-level replication of simian and human immunodeficiency viruses. J. Immunol. 2010; 184:476-87.

Reeves RK, Gillis J, Wong FE, Yu Y, Connole M, Johnson RP. CD16- natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection. Blood 2010; 115:4439-4446.

Reeves RK, Evans TI, Gillis J, Johnson RP. SIV infection induces an expansion of alpha4beta7+ and cytotoxic CD56+ NK cells. J. Virol. 2010; 84:8959-8963.

Reeves RK, Rajakumar PA, Evans TI, Connole M, Gillis J, Wong FE, Kuzmichev YV, Carville A, Johnson RP. Gut inflammation and idoleamine deoxygenase inhibit IL-17 production and induce cytotoxicity in ROR
t+ NKp44+ mucosal NK cells during SIV infection. Blood 2011; in press.



© 2013 by the President and Fellows of Harvard College