This web page was produced as an assignment for an undergraduate course at Davidson College.

A simple change to human Trim5α can restrict HIV-1.

The Human Immunodeficiency Virus (HIV) killed 3.1 million people globally in 2004.

39.1 million more people are still living with the disease. (unaids)

There is no known cure.

On Wednesday, February 25, 2004, the National Institute of Allergy and Infectious Diseases (NIAID) issued a press release titled Scientists Find HIV-Blocking Protein in Monkeys.

The same day, BBC News printed Protein raises hope of HIV block, and CBS News printed HIV-Repelling Monkey Protein ID'ed.

24 hours later, The New York Times had an article titled Cell Protein Gives Monkeys Innate Immunity to H.I.V., Researchers Discover; The San Francisco Chronicle had run Monkey-cell discovery buoys AIDS researchers - Special gene that provides immunity may help humans, and had a short article called Monkey Protein Blocks HIV

Also, Nature no.6077 was distributed. It contained the actual article behind the sweeping news stories, The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys.

In the early 1970s, a gene was discovered in mice that blocked the activity of certain mouse leukaemia viruses (MLVs). The gene, known as Fv1, seemed to produce a protein that could disable invading retroviruses after they had entered the cell but before they had really started reverse-transcription. It was later discovered that the protein was able to attack retroviruses by interacting somehow with their capsid protein "coats." Fv1

The discovery of Fv1 was interesting because it implied cells might each have their own little innate immune system of retrovirus-restricting proteins, in addition to but independant of the systemic immune system's service to the organism as a whole. Researchers later found that not only are protiens that target MLVs present in many human cells, but that they also use the exact same attack on viral capsid proteins as Fv1.

The field has become particularly interesting in the last few years with the realization that the phenomenon of "innate immunity" is much more widespread that was once thought: the genes involved are being noticed in more and more animals, particularly Primates, and they are turning out to have a wider spectrum of specificity than was originally thought, not only able to disrupt the original MLV but also other retroviruses, such as HIV and SIV(Simian Immunodeficiency Virus).

In fact, that's essentially what Dr. Joseph Sodroski and his team of scientists did.




A team of scientists, headed by Dr. Joseph Sodroski and supported by NIAID, were credited with identifying the protein, which is called TRIM5α (TRIM5-alpha), and then verifying its function by testing HIV’s ability to infect cells grown specifically with and without the protein. The release did not provide any of the scientific details behind the discovery, such as how the team initially identified TRIM5α as the protein they suspected would confer immunity.

It did, however, delve briefly into the "life"cycle of the HIV virus and basically what part of that cycle TRIM5α was inserting itself as a molecular monkey wrench. After gaining entry to a cell, "a key preperatory step is the removal, or uncoating, of the protective shell surrounding HIV's genetic material." This coating is called capsid, and the protein TRIM5α, according the the release, "is the first found to specifically target HIV's capsid."

The press release also noted that humans have their own form of TRIM5α. "While it is not as efficient as the simian version, it does have some HIV-blocking ability.'Perhaps this protein could be induced to greater activity, thereby increasing the level of resistance to HIV infection,' says Dr. Sodroski." Alternatively, it was suggested that monkey models of HIV might finally be possible by knocking out their TRIM5α.






Trim5α on the net and in the popular press
Scientific American:
Monkey Protein Blocks HIV (Feb 26, 2004)
TRIM5-alpha (Dec 27 2004 - Mar 30 2005)
NIH news:
Scientists find HIV-blocking protein in monkeys (Feb 25, 2004)

The Body:
New Strategy for Blocking HIV: Trim5-alpha (Nov 24, 2004)
Researchers Identify Protein in Monkey Cells That Blocks HIV; Could Help Scientists Develop Drugs, Vaccine (Feb 26, 2004)

BBC News:
Protein raises hope of HIV block (Feb 25, 2004)
CBS News:
HIV-Repelling Monkey Protein ID'ed(Feb 25, 2004)
San Francisco Chronicle:
Monkey-cell discovery buoys AIDS researchers Special gene that provides immunity may help humans (Feb 26, 2004)
The New York Times:
Cell Protein Gives Monkeys Innate Immunity to H.I.V., Researchers Discover(Feb 26, 2004)
The Washington Times:
Protein resistant to AIDS discovered(Feb 26, 2004)
Trim5α in academic literature

Current Biology:

A Single Amino Acid Change in the SPRY Domain of Human Trim5α Leads to HIV-1 Restriction

current list of relevant articles (on CiteULike)


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