Immunodeficient Parameters in the HIV-1 Transgenic Rat Model
- 1 Seton Hall University, United States
- 2 Weill Cornell Medical Center, United States
Abstract
Recently an HIV-1 transgenic (HIV-1Tg) rat model was created that carries a gag-pol-deleted HIV-1 genome under the control of the HIV-1 viral promoter. However, other viral proteins are expressed in most organs and tissues, and are found in the circulating blood. Since HIV-1 targets the immune system in humans, we examined two immunological parameters, leukocyte-endothelial adhesion (LEA) and inflammatory cytokine production, in 5 mo old HIV-1Tg rats to identify immune functions that may be impaired even before the onset of symptoms of HIV-1 infection. We administered a single injection (i.p.) of the bacterial endotoxin, lipopolysaccharide (LPS, 250 ug/kg), to 5 mo old HIV-1Tg rats, age-matched transgenic control (Tg) rats, and F344/NHsd (F344) control background strain rats. LPS induced an LEA response in both the Tg control and F344 control animals. However, in the HIV-1Tg rats, there was no LEA response to LPS. Following LPS administration, there was significantly greater serum levels of TNF-α and IL-1β, two pro-inflammatory cytokines, in the HIV-1Tg rats compared to the control animals. In contrast, the serum level of IL-10, an anti-inflammatory cytokine, was comparable in the HIV-1Tg, Tg control, and F344 control rats. Our data show that, in the HIV-1Tg rat, there is a negative correlation between the LEA response and the induction of pro-inflammatory cytokines in response to bacterial endotoxin. These findings suggest that the persistent presence of viral proteins may be, at least, partially responsible for the immunodeficiency that occurs with HIV-1 infection, and that the HIV-1Tg rat could be a valid rodent model in which to study various aspects of HIV-1 infection.
DOI: https://doi.org/10.3844/ajidsp.2007.202.207
Copyright: © 2007 Sulie L. Chang, Frank Ocasio and Jose A. Beltran. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Keywords
- Leukocyte-endothelial adhesion
- cytokines
- lipopolysaccharide