Health & Medicine - Posted by Tom Rickey-Rochester on Tuesday, June 29, 2010 16:40 - 4 Comments 
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(1 votes, average: 5.00 out of 5) Loading ...Original HIV infection morphs, but hangs on
Ultrastructural details of a number of HIV virus particles, or virions. (Credit: CDC)
U. ROCHESTER (US)—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.
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The text of this article by Futurity is licensed under a Creative Commons Attribution-No Derivatives License.
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.
It’s 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, it’s not because the 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, says Ha Youn Lee, assistant professor of biostatistics and computational biology at the University of Rochester.
The dynamics in the earliest stage of infection by HIV are incredibly complex, and understanding what happens is crucial for developing a vaccine, she adds.
To do the study, Lee’s team applied a mathematical model to data originally gathered by David O’Connor of 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, Lee says. It allows taking a look at the earliest stages of infection in more depth, and quantifying exactly what is going on in the body. Greater understanding allows for the fine-tuning of 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.
The team also found that SIV creates such mutants in response to the assault by CD8 cells at about the same rate as HIV does.
But the most striking finding is that the original viral genetic sequences are still present in the body months after the initial infection, at a time that scientists call the viral set point, which occurs about two to five months after infection.
It’s a signal of just how difficult it is for the body to eradicate HIV from the body—key portions of the virus have managed to survive despite the immense immune assault.
It’s a surprise that the original virus stays in the body so long, says Stephen Dewhurst, professor of microbiology and immunology, and one of the study authors.
“We know that the virus confronts such a strong response from the body’s immune system that the virus evolves quickly to cope with it,” he says, “yet, the virus is able to establish a reservoir somewhere in the body, where it continues to reproduce and does not have to respond to the threat from the immune system.
The work was funded by the National Institute of Allergy and Infectious Diseases and supported by the University’s Developmental Center for AIDS Research.
More health news from the University of Rochester: http://www.urmc.rochester.edu/news/
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4 Comments
Phoenix
Years ago I remember reading a theory that the appendix, which for years had been considered nothing more than a vestigial organ, was likely a reservoir for desirable gut bacteria that the body used to repopulate the intestines after infection. Now that we know that the initial (and likely more desirable) population of gut flora and fauna are transmitted from mothers to their infants during birth, it makes sense that a reservoir of this initial population might be held in some protected part of the body for future use — analogous to a heirloom seed bank.
As I recall, there was also an implication in the original article that the appendix was able to shield its residents from at least some of the action of antibiotics. I don’t know whether that theory was discredited or not, but, if not, the concept of a viral reservoir protected from the immune system — or maybe even by the immune system — might have a bacterial analogy.
Much of our immune system is focused in and around the intestines. Sounds pretty far-fetched even as I write this, but is there any difference in HIV viral load (or any other aspect of HIV) between treated individuals who have or don’t have an appendix? An ex-post facto study using existing data should be both relatively easy and inexpensive to perform to see if this idea has any merit at all.
Phoenix
Years ago I remember reading a theory that the appendix, which for years had been considered nothing more than a vestigial organ, was likely a reservoir for desirable gut bacteria that the body used to repopulate the intestines after infection. Now that we know that the initial (and likely more desirable) population of gut flora and fauna are transmitted from mothers to their infants during birth, it makes sense that a reservoir of this initial population might be held in some protected part of the body for future use — analogous to an heirloom seed bank.
As I recall, there was also an implication in the original article that the appendix was able to shield its residents from at least some of the action of antibiotics. I don’t know whether that theory was discredited or not, but, if not, the concept of a viral reservoir protected from the immune system — or maybe even by the immune system — might have a bacterial analogy.
Much of our immune system is focused in and around the intestines. Sounds pretty far-fetched even as I write this, but is there any difference in HIV viral load (or any other aspect of HIV) between treated individuals who have or don’t have an appendix? An ex-post facto study using existing data should be both relatively easy and inexpensive to perform to see if this idea has any merit at all.
Jill
To Phoenix
I don’t know if this is exactly what you are inferring, but according to 1 study “Acute appendicitis occurs at higher incidence rates among HIV-infected patients compared with the general population.”
Crum-Cianflone N , Weekes J , Bavaro M. 2008. Appendicitis in HIV-infected patients during the era of highly active antiretroviral therapy. HIV Medicine v9(6) p. 421-426. DOI 10.1111/j.1468-1293.2008.00577.x
I would guess that finding the reservoir where the HIV virus hides is going to be the next big problem. Does the virus alter itself so the body does not recognize it or is there some tissue where it resides in such a form the body identifys the tissue but not the virus? Could it be there are so many modifications of the virus the body ‘forgets’ the original form?