More progress is being made for a cure for HIV

[thwak is T.hawk]

HOORAY!

www.sciencedaily.com/releases/2010/08/100824121022.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29

ScienceDaily (Aug. 24, 2010) — Using a $225,000 microscope, researchers have identified the key components of a protein called TRIM5a that destroys HIV in rhesus monkeys.

The finding could lead to new TRIM5a-based treatments that would knock out HIV in humans, said senior researcher Edward M. Campbell, PhD, of Loyola University Health System.

Campbell and colleagues report their findings in an article featured on the cover of the Sept. 15, 2010 issue of the journal Virology, now available online.

In 2004, other researchers reported that TRIM5a protects rhesus monkeys from HIV. The TRIM5a protein first latches on to a HIV virus, then other TRIM5a proteins gang up and destroy the virus.

Humans also have TRIM5a, but while the human version of TRIM5a protects against some viruses, it does not protect against HIV.

Researchers hope to turn TRIM5a into an effective therapeutic agent. But first they need to identify the components in TRIM5a that enable the protein to destroy viruses. "Scientists have been trying to develop antiviral therapies for only about 75 years," Campbell said. "Evolution has been playing this game for millions of years, and it has identified a point of intervention that we still know very little about."

TRIM5a consists of nearly 500 amino acid subunits. Loyola researchers have identified six 6 individual amino acids, located in a previously little-studied region of the TRIM5a protein, that are critical in the ability of the protein to inhibit viral infection. When these amino acids were altered in human cells, TRIM5a lost its ability to block HIV-1 infection. (The research was done on cell cultures; no rhesus monkeys were used in the study.)

By continuing to narrow their search, researchers hope to identify an amino acid, or combination of amino acids, that enable TRIM5a to destroy HIV. Once these critical amino acids are identified, it might be possible to genetically engineer TRIM5a to make it more effective in humans. Moreover, a better understanding of the underlying mechanism of action might enable the development of drugs that mimic TRIM5a action, Campbell said.

In their research, scientists used Loyola's wide-field "deconvolution" microscope to observe how the amino acids they identified altered the behavior of TRIM5a. They attached fluorescent proteins to TRIM5a to, in effect, make it glow. In current studies, researchers are fluorescently labeling individual HIV viruses and measuring the microscopic interactions between HIV and TRIM5a.

"The motto of our lab is one of Yogi Berra's sayings -- 'You can see a lot just by looking,'" Campbell said.

Campbell is an assistant professor in the Department of Microbiology and Immunology at Loyola University Chicago Stritch School of Medicine. His co-authors are Jaya Sastri, a Stritch graduate student and first author; Christopher O'Connor, a former post-doctorate researcher at Stritch; Cindy Danielson and Michael McRaven of Northwestrn University Feinberg School of Medicine and Patricio Perez and Felipe Diaz-Griffero of Albert Einstein College of Medicine.

So while it's not an all out cure, it does show that progress is being made and that HIV might be cured in hopefully 20 or so years.

[Dr. T is an alien]

There are a number of major issues that occur whenever one tries to treat HIV by attacking the surface proteins of the virus.

1) They are obscenely variable. The structure of the protein only has one region that has high consistency (the portion that identifies and connects to your CD4 proteins). The rest are so variable that you cannot design any treatment unless you did it for each individual (which is prohibitively expensive).

2) You cannot attack the one consistent region of HIV surface proteins because you would destroy the patient's immune system faster than the virus would. CD4 is a vital protein in your immune system because it is a matching component for MHC II proteins (think of them as lego pieces that must fit together to work, and duplo just won't get the job done). HIV mimics MHC II's active site in order to bind to CD4. Anything that can attack the consistent site on HIV surface proteins will also attack the active site of MHC II.

3) Infected cells continually pump out large volumes of HIV virions until the cell finally dies. This means that any treatment will have to be a continuous and unending one.

4) HIV actually has a stage in which it actually attacks a different cell type (primarily early in infection). This means that this treatment can never work prophylacticly, Also, this treatment will select for mutants that fail to come out of that stage, for which this selective treatment might not work.

5) It will only be of use in certain portions of the world. Expenses, politics, local customs, education levels, and ease of use play a huge role in treatment. Any treatment that requires any special storage or process is ineffective for use in any place that is not a developed country. Believe it or not, but the use of antibiotics in South Africa will significantly improve the endemic situation there long before this treatment will. I know that sounds wrong, but adequately treating VD in South Africa will significantly lower the number of new infections. In developed countries one normally does not contract easily, even when exposed. It usually happens through repeat exposure. In nations where VD is not treated, however, exposure equals infection due to the small lesions that are present in the genitals as a result of the VD infection. It makes for ease of transfer directly into the bloodstream.