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Science and Medicine: Retroviruses

David Brown
Washington Post Staff Writer
Tuesday, September 2, 2008 1:00 PM

Washington Post staff writer David Brown and Paul D. Bieniasz, a virologist at the Rockefeller University and the Aaron Diamond AIDS Research Center in New York, were online Tuesday, Sept. 2 at 1 p.m. ET to answer questions about new discoveries about retrovirues.

It's recently been found that eight percent of the human genome is comprised of viruess that once attacked our ancestors, leaving behind the molecular equivalents of DNA fossils.

Read more: In Our Genes, Old Fossils Take On New Roles ( Post, By David Brown, Sept. 1)

A transcript follows.

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David Brown: Greetings chatters. This is the science chat about endogenous retroviruses, more specifically human endogenous retroviruses (HERVs), which were the subject of an article in The Post on Monday, September 1. We are extremely fortunate to have with us today Dr. Paul D. Bieniasz, a virologist with the Aaron Diamond AIDS Research Center and The Rockefeller University, both in New York City. He headed one of the teams that reanimated an endogenous retrovirus, HERV-K from inactivated genes, last year. So let's begin.

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Munich, Germany: Is the process in which retroviruses became part of the human genome similar to the concept and theory of gene therapy?

Paul D. Bieniasz: Yes, one type of experimental gene therapy uses retroviruses to permanently insert genes into cellular DNA. However, this involves somatic cells (eg. blood cells, liver cellss etc.) so that the 'therapy' dies with the host. No experiments have been tried where the germline cells (sperm and Egg) are modified with introduced genes. The consequences of this are viewed as too unpredictable and potentially dangerous.

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Las Vegas, Nevada: I wonder if neuromuscular illnesses such as MD and ALS may have been caused by retrovirues, since these illnesses lack a known cause for over 100 years.

Paul D. Bieniasz: Unlikely. Some forms of these diseases have been shown to be caused by mutations other than retroviral insertion. The epidemiology of these diseases does not match that of an infectious disease. It is theoretically possible that retroviral insertion into the germline could cause gene inactivation and disease but this has not been found in MD and ALS

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Council Bluffs, Iowa: What are the vertabrae lineage? In other words, who is included with chimpanzees and humans? All vertabrae? And do these family ties go back to microscopic sized entities?

David Brown: Actually, DNA sequences that appear to be endogenous retroviruses are in more than just vertebrates. For example, they are also found in insects. The tell-tale sign is a sequence that appears to be an envelope gene, which implies the entity where they gene originated had a phase of life that was outside the cell.

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Laytonsville, Md.: Eight percent of the human genome is made up of "viral fossils". The mitochondrion, a cellular organelle that provides energy to the cell, is thought to be a bacterium that billions of years ago developed an intracellular symbiotic relationship with its host. Could it be possible that the HIV DNA genome that is integrated in the human genome during the silent phase of infection may eventually become another viral fossil? If such were the case, then why not remove the infectious parts of the HIV genome and develop an attenuated vaccine? At the rate we are going investing or wasting billions of dollars with "vaccines" containing denatured viral glycoproteins such as gp160, gp120, etc, I doubt we will ever get closer to developing an HIV vaccine. Of all retroviruses, the SIV/HIV lentiviruses have been the most destructive infectious agents among people and non-human primates. I understand there is a commercially available vaccine construct against a feline retrovirus that was based on that approach.

Just a thought!

Paul D. Bieniasz: HIV does not infect cells of the germline (sperm or egg progenitors) so it is very unlikely to become a viral fossil. This does not really help in terms of tackling the problems of vaccine devolopment, which involve separate issues.

The challenges to developing HIV vaccines are numerous and really outside the scope of this discussion - the effective feline retroviral vaccine involves relatively standard approaches to vaccine developments that have not worked in the case of HIV.

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Washington D.C.: Hello and thanks for taking questions,

My question is involves cancer and retroviruses--

Do you think that as we learn more about cancer, retroviruses will play an even bigger part in carcinogenesis?

Thanks

Paul D. Bieniasz: Its possible, but it seems a little unlikely that known retroviruses will have have an increased impact on carcinogenesis. One known exogenous human retrovirus, HTLV, causes leukemia,somehat rarely. Associations between endogenous retroviruses and cancer have been difficult to firmly establish, and may not exist. My feeling is that retroviruses that have a strong tendency to cause cancer would have been purged from the population by negative selection as humans evolved.

One posiibility is the emergence of new retroviruses in humans. Retroviruses certainly can cause cancer in animals and transission to humans could in principle result in new diseases, including cancer.

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New York, N.Y.: This is fascinating. Where can a layperson learn more about this subject?

David Brown: There has been surprisingly little written in the popular science press about this, given its inherent fascination. There is a somewhat technical account called "The Discovery of Endogenous Retroviruses" by Robin Weiss, in the journal Retrovirology, 2006, volume 3, p. 67. He is the British ressearcher who was one of the discoverers of endogenous retroviruses in the late 1960s or early 1970s. A more recent account about the subject was in The New Yorker on December 3, 2007, called "Darwin's Surprise", by Michael Specter.

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New York, N.Y.: How were these HERVs deactivated? Is it known how the enzyme APOBEC3 kills the genome?

Paul D. Bieniasz: The HERVs were almost certainly inactivated by mostly random, lethal mutations. We found a few HERVs, as well as ERVS in animals that were inactivated by APOBEC3.

The way APOBEC3 works is primarily by causing massive levels of mutation in retroviruses. It is an host cell enzyme that infiltrates retrovirus particles as they emerge from infected cells. Then, when the retrovirus infects a new cell, the APOBEC3 attacks the new viral DNA as it is made by the viral enzyme, reverse transcriptase. In so doing, APOBEC3 changes many of the DNA bases so that they encode non functional viral proteins. Thus, the new cell becomes infected with, in effect, a crippled retrovirus, carrying many mutations that are lethal (to the retrovirus)

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David Brown: Well, it was a short chat but a very interesting one. I want to thank Dr. Paul Bieniasz for spending time on it and offering his expertise. Goodbye until next time.

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