Researchers at UVA School of Medicine have found long-sought answers to questions about HIV transmission, and the findings could lead to new ways to prevent the disease’s spread.
More than 1 million individuals worldwide are infected with HIV every year, even though the virus is not easily transmitted, especially via sex. When transmission occurs, it is usually caused by a single virus that has made it past many different biological and cellular defenses.
UVA researchers have identified what they believe is a critical factor that was previously unknown to be involved in the process. Successful transmission, they believe, is influenced by a protein the virus makes and how that protein interacts with the RNA of the virus. Natural variation in the process, the researchers said, could be a key factor in determining whether HIV is passed on, especially during unprotected vaginal sex.
“Protecting people from getting HIV is a major public health goal,” researcher Dr. Patrick Jackson of UVA’s Thaler Center for AIDS and Human Retrovirus Research said. “Our work on understanding the process of HIV transmission could point the way to better drugs to prevent HIV.”
During untreated HIV infection, many different variations of the virus are made within a single individual. When a new infection happens, just one variant is transmitted. Known as the “transmission bottleneck,” scientists have struggled to explain the phenomena.
UVA researchers, including Jackson, Dr. David Rekosh and Dr. Marie-Louise Hammarskjöld, said the bottleneck may result in part from variations in the viral Rev protein and how it interacts with a part of the viral RNA known as the Rev Response Element (RRE). The interaction is needed for the virus to copy itself in the cytoplasm inside human cells.
The UVA team looked at Rev-RRE activity in viruses during vaginal HIV transmission and found that the viruses that established the new infections tended to show low Rev/RRE activity. That suggests that naturally occurring variations in Rev-RRE activity may determine which viruses start a new infection, and may also allow the virus to adapt to different “fitness landscapes,” which could play a key role in how HIV takes hold inside a new individual.
“This is a new insight into HIV transmission,” Hammarskjöld said. “If the Rev-RRE system is important here, it could also be important for other aspects of HIV disease, including how the virus establishes lifelong infections.”
Researchers said that the new insights into a previously unknown factor in HIV transmission helps us better understand how HIV is spread and could lead to new ways to stop it.
“It’s exciting to connect very fundamental work about how HIV works with issues that matter to patients,” Rekosh said. “This finding highlights the importance of basic research. Answering questions about how things work in the lab often eventually leads to new treatments at the bedside.”
The UVA researchers have published their findings in the scientific journal Open Forum Infectious Diseases. The research was supported by the National Cancer Institute, the National Institutes of Health and UVA via the Myles H. Thaler Research Support Gift, the Myles H. Thaler Professorship and the Charles H. Ross Jr. Professorship.
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Rebecca Barnabi
