First HIV Rat Seen as Best Model for Human Studies

Released: 8/1/2001 12:00 AM EDT
Source: University of Maryland Biotechnology Institute

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(for immediate release)
July 31, 2001

FIRST HIV RAT SEEN AS BEST MODEL FOR HUMAN STUDIES

BALTIMORE, Md.-- With more people living with AIDS than ever before, researchers will welcome a new rat model to study the pathogenesis and the development of new drugs to treating AIDS, say scientists in the July 31 issue of the Proceedings of the National Academy of Sciences.

Scientists at the University of Maryland Biotechnology Institute (UMBI) have engineered laboratory rats for the first time to contain the genome of the AIDS virus HIV-1 except for two genes that make the virus non-infectious. The model cannot transmit the disease to humans.

"The new HIV transgenic rat is an excellent model for studying early and chronic infections, that is, the tracking of the clinical, cellular, and immunologic course of HIV-1 in humans," says senior author of a PNAS paper Joseph L. Bryant, head, Animal Model Division of UMBI's Institute of the Human Virology. "It will be especially effective in testing potential therapeutic strategies against chronic AIDS-associated conditions or syndrome."

Now that HIV anti-retroviral therapy can control the virus, giving longer life to AIDS patients, more of them develop diseases of the kidneys heart pancreas, skin, and other organs and, especially, neurological conditions associated with AIDS, explains Bryant.

"The HIV rat model can now tell us a lot about how these patients develop the diseases. If you understand how the HIV genes are causing these problems in particular organs, researchers can learn how, for example, kidney disease develops in AIDS patients, and they can better learn how to treat it in association with other conditions of the syndrome."

By five to nine months of age, the HIV-1 transgenic rats develop clinical signs similar to those of AIDS in humans, including cataracts, weight loss, skeletal muscle atrophy or "wasting," neurological abnormalities, and respiratory difficulty. Many of the rats also suffered from mild-to-severe skin lesions, kidney disease, and cardiac disorders, all of which have been reported in chronically HIV-infected humans.

Investigations of human immunodeficiency virus (HIV) infection of man have benefited from the study of relevant animal models of the infection and disease, however, the ultimate models use primate species, which are either endangered, not generally available, or expensive to maintain, says Bryant.

The HIV rats are also more efficient than mouse models for blood and tissue specimens, Bryant says. Mice provide only 2 to 3 millimeters of blood, rats 30 to 40 millimeters. Organ studies are also easier with the larger animals, he says.

While HIV transgenic mice produce the highest levels of viral proteins in skin and muscle, according to lead author William Reid, IHV assistant professor, the HIV-gene carrying rats produce viral proteins and RNA in a variety of lymphoid tissues, including lymph nodes, spleen, thymus, and blood. The rats also display cellular and immune irregularities characteristics of HIV-1 infection, he says.

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