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-I± and IL-1I², 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.
Highlights
Human immunodeficiency virus-1 (HIV-1) infection results from the actions of HIV-1 viral proteins, including the envelope glycoprotein 120 and Tat, on targeted cells of the immune system, such as macrophages and T-lymphocytes [1,6]
During in the HIV-1 transgenic (HIV-1Tg) rats compared to the control animals, inflammatory conditions, these leukocytes adhere to the the HIV-1Tg rats failed to exert an leukocyte-endothelial adhesion (LEA) response endothelium of the venules [21] in order to penetrate the following treatment with LPS
The LPS-induced LEA response in the HIV-1 transgenic control (Tg) rats: Leukocyte-endothelial adhesion (LEA) is the initial step in the inflammatory response cascade which allows leukocytes to cross the vascular endothelial cell barrier to go to the site of tissue injury
Summary
Human immunodeficiency virus-1 (HIV-1) infection results from the actions of HIV-1 viral proteins, including the envelope glycoprotein 120 (gp120) and Tat, on targeted cells of the immune system, such as macrophages and T-lymphocytes [1 ,6]. The HIV-1Tg rat seems to mimic the condition of patients given HAART, who have limited (controlled) viral replication, but persistent HIV infection. The HIV-1Tg rats are lower in body weight in comparison to age matched controls They show no signs of retarded growth, and they progressively gain weight similar to the control animals. There are no signs of anhedonia in the inflammatory cytokines They are mainly secreted by HIV-1Tg animals, based on their taste response to macrophages and are important mediators of sucrose [unpublished data]. During in the HIV-1Tg rats compared to the control animals, inflammatory conditions, these leukocytes adhere to the the HIV-1Tg rats failed to exert an LEA response endothelium of the venules [21] in order to penetrate the following treatment with LPS.
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