Viral Immunology

The lab has a long-standing interest in determining the immune factors that determine clinical outcome after viral infection, beginning with the identification of cytolytic CD4+ T cell activity in HIV infected subjects who control the infection via robust immune responses (elite controllers). Our group helped define the ontogeny of cytokine induction in acute HIV infection through examination of serum from infected plasma donors.

For acute viral infections, we were the first to show in humans that levels of regulatory T cells (Tregs) determine disease outcome in West Nile virus infection, with higher levels of Tregs predicting asymptomatic infection in humans and mice. Access to blood donors allows us to identify subjects at the earliest point of infection, prior to symptom onset, through routine blood donor screening for viral RNA or DNA. Current efforts focus on study of HIV elite controllers as well as determining the immune correlates of pathogenic outcome in acute arbovirus infections.

Selected Publications:

Norris PJ, Sumaroka M, Brander C, Moffett HF, Boswell SL, Nguyen T, Sykulev Y, Walker BD, Rosenberg ES. Multiple effector functions mediated by HIV-specific CD4+ T cell clones. J Virol 75(20):9771-9779 PMC114549 (2001).

Norris PJ, Moffett HF, Yang OO, Kaufmann DE, Clark MJ, Addo MM, Rosenberg ES. Beyond help: Direct effector functions of HIV-1-specific CD4+ T cells. J Virol 78(16):8844-51 PMC479080 (2004).

Lanteri, MC, Heitman JW, Owen RE, Busch TA, Gefter N, Kiely N, Kamel HT, Tobler LH, Busch MP, and Norris PJ. Comprehensive analysis of West Nile virus T cell responses in human infection. J Infect Dis 197(9):1296-1306 (2008).

Stacey AR*, Norris PJ*, Qin L, Haygreen EA, Taylor E, Heitman J, Lebedeva M, DeCamp A, Li D, Grove D, Self SG, Borrow P. Induction of a striking systemic cytokine cascade prior to peak viremia in acute HIV-1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol 83(8):3719-3733 PMC2663284 (2009).

Lanteri MC, O’Brien KM, Cameron MJ, Purtha WE, Lund JM, Owen RE, Heitman JW, Custer B, Hirschkorn DF, Tobler LH, Kiely N, Prince HE, Ndhlovu LC, Nixon DF, Kamel HT, Kelvin DJ, Busch MP, Rudensky AY, Diamond MS*, Norris PJ*. Tregs control the development of symptomatic West Nile virus infection. J Clin Invest 119(11):3266-77 PMC2769173 (2009).

Owen RE, Heitman JW, Hirschkorn DF, Lanteri MC, Biswas HH, Martin JN, Krone MR, Deeks SG, Norris PJ and the NIAID Center for HIV/AIDS Vaccine Immunology. HIV+ elite controllers have low levels of HIV-specific T cell activation yet maintain strong, polyfunctional T cell responses. AIDS 24(8):1095-105 PMC2972651 (2010).

Keating SM, Golub ET, Nowicki M, Young M, Anastos K, Crystal H, Cohen MH, Zhang J, Greenblatt RM, Desai S, Wu S, Landay AL, Gange SJ, Norris PJ. The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of US women. AIDS 25(15): 1823-32 PMC3314300 (2011).

Keating SM, Heitman JW, Wu S, Deng X, Stacey AR, Zahn RC, de la Rosa M, Finstad SL, Lifson JD, Piatak M, Gauduin MC, Kessler BM, Ternette N, Carville A, Johnson RP, Desrosiers RC, Letvin NL, Borrow P, Norris PJ*, Schmitz JE*. Magnitude and quality of cytokine and chemokine storm during acute infection distinguish non-progressive simian immunodeficiency virus infections of nonhuman primates. J Virol 90(22):10339-50 (2016).

*These authors contributed equally to this work.