A powerful protein that tricks the immune system into believing cells are not infected by HIV has been the subject of an intense investigation by a team of global researchers.
The protein – called Nef – and its role in affecting the disease progression in people with HIV – are now better understood thanks to the critical role played by team member Mitchell Mumby, a PhD candidate supervised by Jimmy Dikeakos, a professor in the department of microbiology and immunology at Schulich School of Medicine & Dentistry.
Mumby will present his work in isolating various Nef sequences to a multidisciplinary session at the Canadian Conference on HIV/AIDS Research (CAHR Conference), the largest gathering of HIV researchers in Canada, which will be held at RBC Place London April 25 to 28. The student researcher will also be named as an Academic Scholarship Winner – Basic for the top-ranked abstract by a student.
“It’s a privilege to give an oral presentation because it means the committee has determined your work is worth the extra time for discussion. For me, that’s very validating,” he said. “What’s also special is that this has been selected for a key population; in this case people from Uganda who are marginalized in the areas of research and access to antiretroviral drugs.”
Mumby’s work involved isolating various sequences of the potent viral HIV-1 accessory protein from a cohort of people with HIV from the Rakai Health Sciences Program, located in the Rakai region of Uganda. His studies showed that Nef works by removing a critical protein called major histocompatibility class I (MHC-I) from cells infected by HIV-1 and fooling the immune system into thinking the virus is gone.
While people with HIV recover with antiretroviral drugs, they are not cured. The drugs target the active HIV, but not the latent HIV. When patients stopped taking the drugs, the virus reactivates and returns with a vengeance, said Mumby.
“This study is pivotal as it demonstrates that targeting Nef may represent a viable strategy to decrease the size of the latent HIV-1 reservoir in people with HIV during long-term treatment,” said Dikeakos. The global team included Jessica Prodger, and Art Poon, both from the department of microbiology and immunology, and Dr. Andrew Redd from the National Institutes of Health.
The conference will bring more than 550 researchers and others interested in HIV research from all disciplines to London to share research and participate in five plenary sessions, special panel discussions and abstract presentations. Individuals from other scientific disciplines and private sector representatives will also be present.
Schulich Medicine & Dentistry and Lawson faculty are taking lead roles on the scientific committee for the conference, which recognizes the “outstanding group of HIV researchers we have here at Western,” said Dikeakos, who is a basic science track co-chair, and whose research examines the movement of proteins within HIV-1 infected and non-infected cells.
Also, on the scientific committee are Prodger, Canada Research Chair, Genital Immunology and STI Prevention, and co-chair of the epidemiology and public health sciences track; and Dr. Michael Silverman, professor of medicine and infectious diseases and co-chair of the clinical sciences track.
One of the major topics discussed in Prodger’s track will be the use of race-based data in improving HIV outcomes.
“This is a difficult topic, as even the first step – defining race in datasets – is fraught with difficulties,” said Prodger, whose work focuses on developing novel strategies for HIV prevention and cure in Africa. “However, when someone is racialized by society (including the health-care system) it can have substantial impacts on their risk of acquiring HIV and their ability to access treatment and care. Ignoring race because it is hard to capture is not a solution to this problem.”
Silverman is focusing on the impact of addiction in women and their risk for infectious complications of drug use and the importance of screening for anal cancer in patients with HIV.
“I hope this conference will help to encourage our efforts to accelerate roll-out of HIV prevention efforts as well as develop strategies to have early detection and thereby cure of anal cancer,” Silverman said.
The conference brings together researchers who are on the cutting edge of HIV research in many fields, said conference co-chair Eric Arts, professor of microbiology and immunology and Canada Research Chair in HIV Pathogenesis and Viral Control.
“This is an amazing opportunity to feature the work of researchers at Schulich Medicine & Dentistry and across our entire campus. We have extraordinary facilities here and I’m excited to see them showcased at a world-class event. This will be an extraordinary moment for Western and the City of London,” said Arts, who is also executive director of Western’s Imaging Pathogens for Knowledge Translation (ImPaKT) Facility.
Equitable outcomes for all
Isaac Luginaah, a Western geography and environment professor, will deliver a plenary talk on epidemiology and public health at CAHR 2024, focused on equity, diversity and inclusion in HIV/AIDS research. An expert in health geography, Luginaah has a long history working with medical practitioners and government leaders in Canada, Kenya, Ghana and Nigeria, especially those affected by HIV/AIDS.
HIV transmission, he noted, has been declining in Canada over the last two decades, but this trend masks a disturbing reality.
“Black communities bear a hugely disproportionate burden of the epidemic, while declining transmission is limited to white Canadians, especially white gay men,” said Luginaah. “Canada is moving in the right direction for white Canadians given the overall declining rates, but not others. Indigenous and Black communities are not seeing the same rates of decline.”
Luginaah says this racial divide is, unfortunately, a predictable outcome of systemic inequalities that continue to permeate Canadian society, including all levels of government, despite a decades-long public effort to eradicate racism across the country.
Over the same period, HIV/AIDS research has made significant strides, in Canada and abroad, leading to improved treatments and prevention strategies. However, the advancement of equity, diversity, inclusion and decolonization (EDID) in HIV research continues to lag behind.
“In Canada, basic things like race-based data are frequently not collected or collected inadequately. For instance, race and/or ethnicity data was reported for only 45.3 per cent of first-time HIV diagnoses across the country in 2021. And for Manitoba and Quebec, zero race and/or ethnicity data was reported,” said Luginaah. “This lack of data also eliminates the need for action.”
Again, Luginaah says Canada is making great progress in the fight against HIV/AIDS but there is far more work to be done and we should look to other countries for direction.
“Countries that seem to have done relatively well, have targeted communities that are most at risk, with a strong engagement of local community partners in countries like the United States and South Africa,” said Luginaah.
In his CAHR plenary talk, Luginaah will address the challenges and opportunities of integrating EDID in HIV/AIDS research, while highlighting examples of recently completed and ongoing studies.
“The ultimate goal is to celebrate the possibilities of designing and implementing innovative research that addresses HIV disparities and ensures equitable outcomes for all,” said Luginaah.