Alpha-4 beta-7 integrin in HIV pathogenesis

2017

Challenge

In most people infected with human immunodeficiency virus (HIV), their immune system cannot control HIV infection. They need drug cocktails called combination antiretroviral therapy (cART) to defend against the virus. When people stop cART treatment, their immune system again cannot control the infection. They can also become resistant to cART and have lasting side effects. Researchers want to identify ways to control HIV infection without the need for cART.

Advance

IRP researchers led by Anthony Fauci, M.D., in collaboration with Emory University experimentally induced sustained remission of the simian immunodeficiency virus (SIV), a form of HIV that infects non-human primates, in infected monkeys using an antibody against the α4β7 integrin cellular receptor. IRP researchers led by Paolo Lusso, M.D., Ph.D., also showed that, in HIV-positive individuals, α4β7 integrin is incorporated into HIV virions, viral particles that transmit the virus to cells. This suggests that the antibody treatment may facilitate the induction of protective immune responses against HIV and/or directly interfere with the virus’ ability to target intestinal tissues.

Impact

The α4β7 integrin antibody-based treatment regimen led to the near-complete replenishment of key immune cells that SIV had destroyed, something unachievable with cART alone. A clinical trial testing the treatment regimen in HIV-infected people is underway at the NIH Clinical Research Center in Bethesda, Maryland (ClinicalTrials.gov Identifier: NCT02788175).

Publications

Guzzo C, Ichikawa D, Park C, Phillips D, Liu Q, Zhang P, Kwon A, Miao H, Lu J, Rehm C, Arthos J, Cicala C, Cohen MS, Fauci AS, Kehrl JH, Lusso P. (2017). Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing. Sci Immunol. May 12;2(11).

Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, Sidell N, Kane MA, Yu J, Jones JW, Santangelo PJ, Zurla C, McKinnon LR, Arnold KB, Woody CE, Walter L, Roos C, Noll A, Van Ryk D, Jelicic K, Cimbro R, Gumber S, Reid MD,  Adsay V, Amancha PK, Mayne AE, Parslow TG, Fauci AS, Ansari AA. (2016). Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy. Science. Oct 14;354(6309):197-202.