BC-CfE and SFU researchers uncover viral features that may contribute to global differences in HIV pathogenesis

The result of a longstanding collaboration between SFU and the BC-CfE, new research from the laboratories of Drs. Mark Brockman and Zabrina Brumme was recently published in the respected scientific journal PLoS Pathogens.

The paper entitled “Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5” looks at the genetic and functional diversity of the HIV protein Nef, and how this key viral protein interacts with proteins inside human cells. The research was led by BC-CfE Scientific Associate Mark Brockman, who is also an Associate Professor in the Faculty of Health Sciences and the Department of Molecular Biology and Biochemistry in the Faculty of Sciences at Simon Fraser University.

Our cells are equipped with proteins called “restriction factors” that protect us from viral infection. For this reason, viruses encode proteins that block these restriction factors. HIV encodes a number of such proteins, of which the most well-studied is Nef. Nef blocks a number of restriction factors, two of which are named Serine incorporator (SERINC) protein 3 and SERINC 5. These SERINC proteins are expressed on human cells and become incorporated into new viral particles, where they dampen HIV’s ability to infect new cells and attenuate pathogenesis. The Nef protein removes SERINC3 and SERINC5 from the infected cell surface, thereby enhancing HIV’s ability to spread.

HIV is a very genetically diverse virus, with many different strains circulating worldwide. Brockman’s team wanted to understand the impact of HIV genetic diversity on Nef’s ability to block the SERINC proteins. To address this, they isolated hundreds of HIV Nef variants from people living with HIV worldwide and tested the ability of each variant to counteract the human SERINC proteins. They discovered that Nef isolates from circulating viral strains differed markedly in their ability to antagonize SERINC3 and SERINC5.

They were also able to pinpoint specific naturally occurring mutations in Nef that affected these functions.

These findings uncover viral features that may contribute to global differences in HIV pathogenesis and provide new insights that can inform future studies.

Researchers at other global institutes also contributed to this research, including the University of KwaZulu-Natal (South Africa), Mbarara University of Science and Technology (Uganda), UCSF and others.

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