Despite Countless Changes, Original HIV Infection Lurks Within

Scientists have been surprised to learn that, despite thousands of changes that viruses like HIV undergo in rapid fashion to evade the body’s immune system, the original version that caused the infection is still present in the body months later.

The finding, published in the June issue of the Journal of Virology, is the result of an uncommonly detailed look at the cat-and-mouse action that takes place in an organism shortly after infection. The work is aimed at understanding the earliest stages of infection by HIV more thoroughly, to help scientists develop ways either to quash the infection outright or to develop a vaccine to prevent infection.

The research, which was conducted by scientists at the University of Rochester Medical Center, is based on an analysis of more than 100,000 genetic snippets of a virus known as SIV, or simian immunodeficiency virus, which infects monkeys and is a close cousin of HIV.

While HIV has flummoxed scientists for nearly three decades, that’s certainly not because our immune system fails to respond. Rather, within two or three weeks of infection, the onslaught of immune cells puts the virus on the run to such an extent that the virus must mutate rapidly to evade the body’s defenses.

HIV changes quickly and continually, creating thousands and thousands of mutated versions of itself in a process called “viral escape.” The virus changes; the immune cells hunting it down change in response; and the virus changes again, and so on, in a kind of molecular arms race.

“Viral escape is a significant phenomenon in HIV – it’s what allows HIV to elude the immune system,” said Ha Youn Lee, Ph.D., the assistant professor in the Department of Biostatistics and Computational Biology who led the project.

“The dynamics in the earliest stage of infection by HIV are incredibly complex, and understanding what happens is crucial for developing a vaccine,” Lee added.

To do the study, Lee’s team applied a mathematical model to data originally gathered by David O’Connor, Ph.D., at the University of Wisconsin at Madison, who studies how SIV evolves. Lee’s team analyzed the genetic features of three key sections of the SIV genome as they changed during the first few months of infection in eight macaque monkeys, part of an effort to quantify how quickly the process of viral escape occurs.

The research took advantage of a method known as ultradeep sequencing, which provides hundreds or thousands of glimpses of a single genetic change, compared to approximately 50 or so looks using conventional methods.

“This new technology is very exciting,” said Lee. “It allows us to look at the earliest stages of infection in more depth than we could otherwise, and to quantify exactly what is going on in the body. If we can understand it more completely, we can fine-tune vaccines under development.”

As expected, the team found that immune cells known as CD8+ T-lymphocytes, also known as cytotoxic T cells, are a powerful force in the life of SIV when it first causes infection. While scientists have known that the CD8 attack on the virus is strong, the latest work quantifies the body’s response. They found that the original portions of the virus degrade 400 times faster in response to CD8 cells than they would have if those cells weren’t a factor – what scientists call significant “selective pressure” on the virus.