BALTIMORE, Md.-- With more people living with AIDS than ever before, a new rat model will benefit researchers studying the pathogenesis and the development of new drugs to treat AIDS and related diseases, according to a report in this week's 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," quotes senior author of a PNAS paper, Joseph L. Bryant, head, Animal Model Division of UMBI's Institute of 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, states Dr. J. C. Hunter-Cevera, president of UMBI. "We are very excited about the new potential studies with the IHV transgenic rat model that Dr. Bryant and his team at IHV have developed."
In addition, the HIV rats are also more efficient than mouse models for blood and tissue specimens. Mice provide only 2 to 3 millimeters of blood, rats 30 to 40 millimeters. Organ studies are also easier with the larger animals.
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.
The University of Maryland Biotechnology Institute was mandated by the state of Maryland legislature in 1985 as "a new paradigm of state economic development in biotech-related sciences." With five major research and education centers across Maryland, UMBI is dedicated to advancing the frontiers of biotechnology. The centers are the Center for Advanced Research in Biotechnology in Rockville; Center for Agricultural Biotechnology in College Park; and Center of Marine Biotechnology, Medical Biotechnology Center, and the Institute of Human Virology, all in Baltimore.