Scientists identify human proteins that may fuel HIV/AIDS transmission
Amyloid fibrils in semen, shown here in red, enhance HIV infection by helping HIV -- shown in green -- find and attach to its target, CD4 T white blood cells. Credit: Nadia Roan/Gladstone Institutes
Scientists at the Gladstone Institutes have discovered new protein fragments in semen that enhance the ability of HIV, the virus that causes AIDS, to infect new cells -- a discovery that one day could help curb the global spread of this deadly pathogen.
HIV/AIDS has killed more than 25 million people around the world since first being identified some 30 years ago. In the United States alone, more than one million people live with HIV/AIDS at an annual cost of $34 billion.
Previously, scientists in Germany discovered that HIV transmission is linked to the presence of an amyloid fibril in semen. This fibril -- a small, positively charged structure derived from a larger protein -- promotes HIV infection by helping the virus find and attach to its target: CD4 T white blood cells. In tomorrow's issue of Cell Host & Microbe, researchers in the laboratory of Warner C. Greene, MD, PhD, who directs virology and immunology research at Gladstone, describe a second type of fibril that also has this ability.
These findings may spur efforts to slow the spread of HIV/AIDS. Prevention has recently focused on microbicides; chemical gels that, when used by women during sexual intercourse, block HIV infection. But while early microbicides had some success -- reducing infection by an average of 39%more recent trials have failed and devising a truly potent microbicide remains a top priority.
"Today's microbicides may be failing because, while they do target the virus itself, they don't block the virus from interacting with the natural infection-enhancing components of semen," said Nadia R. Roan, PhD, the paper's first author and a research scientist at Gladstone, an independent and nonprofit biomedical-research organization. "Now that we more fully understand how HIV hijacks these components to promote its own infection, we are one step closer to developing a microbicide that can more effectively stop HIV."
Sexual transmission accounts for the vast majority of HIV infections, and semen is the virus' key mode of transport. Earlier studies by Drs. Roan and Greene revealed the mechanism by which a positively charged fibril in semen -- called SEVI -- attracts HIV like a magnet, binding to the negatively charged HIV and helping to infect CD4 T cells. Here, they set out to investigate whether other components of semen also played a part.
In laboratory experiments on human semen samples, they identified a second set of fibrils -- derived from larger proteins called semenogelins -- that enhance HIV infection just as SEVI does. Removing these and other positively charged components from semen diminished HIV's ability to infect CD4 T white blood cells. Further confirming the role of these fibrils in promoting HIV infection, Drs. Roan and Greene found that semen samples from men who are naturally deficient in semenogelins -- a disorder called ejaculatory-duct obstruction -- also had a limited ability to enhance HIV infection.
"Our experiments suggest that fibrils derived from semenogelins -- the major component of semen -- are integral to enhancing HIV infection in semen," said Dr. Roan. "But we are intrigued by their natural, biological function as well. The fact that these fibrils are found in male reproductive organs could point to an evolutionary role in fostering fertilization -- something we're currently exploring."
"We hope that this research paves the way for the next-generation of microbicides that can both neutralize these fibrils and attack the virus," said Dr. Greene, who is also a professor of medicine, microbiology and immunology at the University of California, San Francisco, with which Gladstone is affiliated. "This type of one-two punch in a microbicide -- what current products lack -- could finally give women real protection against HIV's deadly attack."
Provided by Gladstone Institutes
- Scientists identify target that may inhibit HIV infectivity Jan 04, 2010 | not rated yet | 0
- Non-stick coating of a protein found in semen reduces HIV infection Sep 23, 2010 | not rated yet | 0
- Cream with green tea extract hinders HIV transmission: study May 19, 2009 | not rated yet | 0
- Targeting amyloid to stop HIV Sep 28, 2010 | not rated yet | 0
- Human testis harbors HIV-1 in resident immune cells Nov 27, 2006 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
HIV & AIDS 16 hours ago | 5 / 5 (3) | 0 |
Detection of HIV antibodies is used to diagnose HIV infection and monitor trials of experimental HIV/AIDS vaccines. New, more sensitive detection systems being developed use microspheres to capture HIV antibodies ...
HIV & AIDS May 23, 2013 | 5 / 5 (1) | 0
(HealthDay)—For HIV-infected individuals with recurrent Clostridium difficile infection, fecal microbiota therapy is feasible, according to a letter published in the May 21 issue of the Annals of Intern ...
HIV & AIDS May 22, 2013 | not rated yet | 0
Canadian health authorities lifted Wednesday what was effectively a ban on gay men giving blood, announcing new rules making men who have not had sex with men in the past five years eligible.
HIV & AIDS May 22, 2013 | not rated yet | 1
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
10 hours ago | 3 / 5 (2) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
13 hours ago | 3.7 / 5 (3) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
14 hours ago | 5 / 5 (4) | 0 |
How can healthy people who hear voices help schizophrenics? Finding the answer for this is at the centre of research conducted at the University of Bergen.
16 hours ago | 4 / 5 (2) | 2
(Medical Xpress)—The way Alzheimer's disease is portrayed by advocacy groups and the media is having undue influence on the euthanasia debate, according to a Deakin University nursing ethics professor.
17 hours ago | not rated yet | 2
(Medical Xpress)—Patients with diabetes who are depressed are much more likely to develop episodes of dangerously low blood sugars, or hypoglycemia, than are those who are not depressed, a new study has ...
17 hours ago | not rated yet | 0 |