The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART

Peng, Jinsong; Vigorito, Michael; Liu, Xiangqian; Zhou, Dunjing; Wu, Xue-Ru; Chang, Sulie L.

doi:10.1016/j.jneuroim.2009.09.014

Cited by 108 publications

(158 citation statements)

References 25 publications

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“…The HIV-Tg group also displayed some degrees of nitrosative stress at the systemic and cardiac tissue level. Overall, our findings are consistent with the published observation that HIV gene expression alone can exert systemic oxidative stress that is likely due to the known pro-oxidative properties of gp 120, TAT, and Nef, which are 3 of the remaining 7 genes expressed in HIV-Tg rats [14,15,16]. …”

Section: Discussionsupporting

confidence: 91%

“…To determine the effects of HIV expression, we chose to use the well-established HIV-1 Transgenic (Tg) rat model, which expresses 7 of the 9 HIV genes, except for gag and pol which are responsible for infectivity [11,14,15]. The remaining 7 genes carry most of the proteins responsible for the eventual development of AIDS symptoms, but without the complications of infectivity [14,15,16]. …”

Section: Introductionmentioning

confidence: 99%

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Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg

Mak

Chmielinska

Spurney

et al. 2018

IJMS

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Chronic effects of a combination antiretroviral therapy (cART = tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation were assessed. cART (low doses) elicited no significant effects in normal rats, but induced time-dependent oxidative/nitrosative stresses: 2.64-fold increased plasma 8-isoprostane, 2.0-fold higher RBC oxidized glutathione (GSSG), 3.2-fold increased plasma 3-nitrotyrosine (NT), and 3-fold elevated basal neutrophil superoxide activity in Tg rats. Increased NT staining occurred within cART-treated HIV-Tg hearts, and significant decreases in cardiac systolic and diastolic contractile function occurred at 12 and 18 weeks. HIV-1 expression alone caused modest levels of oxidative stress and cardiac dysfunction. Significantly, cART caused up to 24% decreases in circulating Mg in HIV-1-Tg rats, associated with elevated renal NT staining, increased creatinine and urea levels, and elevated plasma substance P levels. Strikingly, Mg-supplementation (6-fold) suppressed all oxidative/nitrosative stress indices in the blood, heart and kidney and substantially attenuated contractile dysfunction (>75%) of cART-treated Tg rats. In conclusion, cART caused significant renal and cardiac oxidative/nitrosative stress/injury in Tg-rats, leading to renal Mg wasting and hypomagnesemia, triggering substance P-dependent neurogenic inflammation and cardiac dysfunction. These events were effectively attenuated by Mg-supplementation likely due to its substance P-suppressing and Mg’s intrinsic anti-peroxidative/anti-calcium properties.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg

Mak

Chmielinska

Spurney

et al. 2018

IJMS

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show abstract

“…This animal model possesses human viral genes, including the HIV-1 pro-virus, but with the deletion of the gag and pol replication genes. The HIV-1Tg rat exhibits similar clinical manifestations as HIV-positive humans, including wasting, skin lesions, cataracts, neurological and respiratory impairment, and changes in the immune system [17]–[20], suggesting that the HIV-1Tg rat model is useful for studying HIV-1-infected patients on highly active anti-retroviral therapy (HAART) [21]. In the last decade, many reports have demonstrated that the HIV-1Tg rat is also a valuable model for studying neuroAIDS [20], [22], [23].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Transgenic Rats Display Alterations in Immunophenotype and Cellular Responses Associated with Aging

Abbondanzo

Chang

2014

PLoS ONE

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Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

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“…The assessments were planned to be conducted from 2 to 8 months of age, antecedent to the documented neurological symptoms or clinical signs of wasting (Peng et al 2010). It was hypothesized that subtle alterations in PPI would be detected early in the progression of the expression of the HIV-1 transgene, as are detected in HIV-1+ individuals.…”

Section: Introductionmentioning

confidence: 99%

Time and time again: Temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat

Moran¹,

Booze²,

Mactutus³

2014

Neurotoxicology and Teratology

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The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART

Cited by 108 publications

References 25 publications

Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg

Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg

HIV-1 Transgenic Rats Display Alterations in Immunophenotype and Cellular Responses Associated with Aging

Time and time again: Temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat

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