Thursday, 20 July 2017 16:25

Antibodies from elite HIV controllers activate the ADCC immune response

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Published in mBiosphere

Since before the introduction of effective therapeutic drugs for HIV/AIDS, some HIV-infected individuals have been able to control the viral infection and maintain a healthy immune system—sometimes for decades. Scientists have long wanted to understand how the immune systems of these ”elite controllers” (EC) maintain low viral replication, with the hope of gaining insights that could translate into therapies for other HIV-infected people. A new Journal of Virology study demonstrates that a difference in immune system responses contributes to protection from progressive infection.

JVirology: HIV-1 Env- and Vpu-specific antibody-dependent cellular cytotoxicity responses associated with elite control of HIV

Antibody responses have been widely studied in HIV patients, but most studies have concentrated on broadly neutralizing antibodies that recognize the HIV Env protein, a glycoprotein found in the membrane of HIV virions. Neutralizing antibodies bind and block the virus from attaching to a new host cell, effectively curtailing the infectious viral life cycle. Neutralizing antibodies toward the Env protein have been difficult to identify due to the high mutation rate within the env gene. Antibodies that help immune cells recognize and attack infected cells through the antibody-dependent cellular cytotoxicity (ADCC) response can target Env or other HIV proteins such as Pol or Vpu. Previous research had shown that HIV-infected fast and slow progressors have different ADCC responses, and in the current study, they further tested the ADCC responses of EC group members. 

To investigate the difference in immune control, a scientific team led by first author Vijaya Madhavi and senior scientist Ivan Stratov collected samples from both viremic and EC HIV patient volunteers, none of whom were taking antiretroviral drugs at the time of sampling. Antibodies isolated from the EC patients mediated more ADCC killing of HIV-infected cells than did antibodies from viremic patients, confirming a role for ADCC in control of HIV infection.

ECs had more total anti-Env and anti-Vpu antibodies than the viremic subjects, and these antibodies from ECs were more likely to bind an antibody receptor, FcγRIIIa, found on some immune cells. Antibodies binding Fc receptors help activate these immune cells, such as natural killer (NK) cells, to eradicate infected cells. When testing patient antibodies for NK cell activation, antibodies from EC patients were better able to induce IFNγ and CD107a expression. IFNγ plays an important antiviral role, while CD107a (also called LAMP1) plays a role in NK cell degranulation, a mechanism used to attack HIV-infected T cells.

Some scientists point to the partially successful RV144 trial, a clinical trial for an HIV vaccine, as a basis for the controlling role of ADCC in HIV infection (some scientists, it should be pointed out, are skeptical of the RV144 trial success). Understanding how ECs control HIV may help scientists design better anti-retroviral drugs—or better, a more effective vaccine. Though the World Health Organization  announced this week that 50% of HIV-infected individuals worldwide are now taking life-saving antiretroviral drugs, there’s still a large population who need treatment, and an even larger at-risk population. Understanding ADCC-mediated killing of HIV-infected cells may lead to an effective vaccine that could help both of these groups.

Photo credit: Human NK cell

Last modified on Thursday, 20 July 2017 16:36
Julie Wolf

Julie Wolf is the ASM Science Communications Specialist. She contributes to the ASM social media and blog network and hosts the Meet the Microbiologist podcast. She also runs workshops at ASM conferences to help scientists improve their own communication skills. Follow Julie on Twitter for more ASM and microbiology highlights at @JulieMarieWolf.

Julie earned her Ph.D. from the University of Minnesota, focusing on medical mycology and infectious disease. Outside of her work at ASM, she maintains a strong commitment to scientific education and teaches molecular biology at the community biolab, Genspace. She lives in beautiful New York City.