Adult neurogenic deficits in HIV-1 Tg26 transgenic mice

Putatunda, Raj; Zhang, Yonggang; Li, Fang; Yang, Xiaofeng; Barbe, Mary F.; Hu, Wenhui

doi:10.1186/s12974-018-1322-2

Cited by 27 publications

(32 citation statements)

References 82 publications

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“…Different research groups have used Tg mice extensively for studies related to HIV-associated nephropathy. To list a few, Tg26 and its variants, as well as CD4/HIV Tg mice and variants, have been used [42]. Tg26 is a transgenic mouse which expresses seven of the nine HIV proteins under the control of a viral LTR promoter.…”

Section: Human Immuno Deficiency Virusmentioning

confidence: 99%

See 1 more Smart Citation

Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections

Krishnakumar

Durairajan

Alagarasu

et al. 2019

Viruses

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Well-developed mouse models are important for understanding the pathogenesis and progression of immunological response to viral infections in humans. Moreover, to test vaccines, anti-viral drugs and therapeutic agents, mouse models are fundamental for preclinical investigations. Human viruses, however, seldom infect mice due to differences in the cellular receptors used by the viruses for entry, as well as in the innate immune responses in mice and humans. In other words, a species barrier exists when using mouse models for investigating human viral infections. Developing transgenic (Tg) mice models expressing the human genes coding for viral entry receptors and knock-out (KO) mice models devoid of components involved in the innate immune response have, to some extent, overcome this barrier. Humanized mouse models are a third approach, developed by engrafting functional human cells and tissues into immunodeficient mice. They are becoming indispensable for analyzing human viral diseases since they nearly recapitulate the human disease. These mouse models also serve to test the efficacy of vaccines and antiviral agents. This review provides an update on the Tg, KO, and humanized mouse models that are used in studies investigating the pathogenesis of three important human-specific viruses, namely human immunodeficiency (HIV) virus 1, influenza, and dengue.

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Section: Human Immuno Deficiency Virusmentioning

confidence: 99%

“…Tg26 is used to study the long-term effect of HIV proteins on the host. Tg mouse models which express the entire genome or selected genes of HIV have given productive results and information on pathogenesis [42].…”

Section: Human Immuno Deficiency Virusmentioning

confidence: 99%

Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections

Krishnakumar

Durairajan

Alagarasu

et al. 2019

Viruses

View full text Add to dashboard Cite

show abstract

“…No expression was found in lung endothelial and epithelial cells. A transgenic mouse model has been used to study the long-term effects of viral proteins on the host [19]. This model is clinically relevant for people with cART-controlled HIV-1 infections, which lack viral replication but undergo the persistent stress of viral protein exposure.…”

Section: Introductionmentioning

confidence: 99%

Oxygen Levels Affect Macrophage HIV-1 Gene Expression and Delay Resolution of Inflammation in HIV-Tg Mice

Jerebtsova

Ahmad

Kumari

et al. 2020

Viruses

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While antiretroviral therapy increases the longevity of people living with HIV (PLWH), about 30% of this population suffers from three or more concurrent comorbidities, whose mechanisms are not well understood. Chronic activation and dysfunction of the immune system could be one potential cause of these comorbidities. We recently demonstrated reduced macrophage infiltration and delayed resolution of inflammation in the lungs of HIV-transgenic mice. Additionally, trans-endothelial migration of HIV-positive macrophages was reduced in vitro. Here, we analyze macrophages' response to LPS challenge in the kidney and peritoneum of HIV-Tg mice. In contrast to the lung infiltration, renal and peritoneal macrophage infiltrations were similar in WT and HIV-Tg mice. Higher levels of HIV-1 gene expression were detected in lung macrophages compared to peritoneal macrophages. In peritoneal macrophages, HIV-1 gene expression was increased when they were cultured at 21% O 2 compared to 5% O 2 , inversely correlating with reduced trans-endothelial migration at higher oxygen levels in vitro. The resolution of macrophage infiltration was reduced in both the lung and the peritoneal cavity of HIV-Tg mice. Taken together, our study described the organ-specific alteration of macrophage dynamics in HIV-Tg mice. The delayed resolution of macrophage infiltration might constitute a risk factor for the development of multiple comorbidities in PLWH.

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“…The HIV-1 Tg26 mouse model is representative of the long-term effects induced by viral proteins on the host and clinically relevant to ART-controlled HIV-1 patients [24]. Recent studies conducted by Putatunda et al, 2018 demonstrated that compared to wild-type (WT) mice, HIV-1 Tg26 mice have neurological de cits both in the early and late stages.…”

Section: Introductionmentioning

confidence: 99%

7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder

Bryant

Andhavarapu

Bever

et al. 2020

Preprint

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Background: The combined antiretroviral therapy (cART) era has significantly increased the lifespan of HIV patients, turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In HIV+ patients, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile.Methods: We investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. We immunohistochemically stained brain tissue sections from vehicle-treated wild type (WT), vehicle-treated Tg26, and DHF (5 mg/kg, i.p)-treated Tg26 mice to examine activation of TrkB and downstream signaling, expression of HIV-1 chemokine co-receptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. A one-way ANOVA with a Bonferroni Comparison post-hoc test was performed to analyze the data sets. Results: In the brain regions of Tg26 mice, we observed astrogliosis, increased CXCR4 and CCR5 expression, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB-Akt-NFkB signaling pathway in mediating these pathological hallmarks.Conclusions: Our study provides an overview of how targeting BDNF-TrkB signaling in the pathophysiology of HAND may be relevant for future therapies, and sheds light on 7,8 Dihydroxyflavone as a potential adjunct therapeutic agent to current antiviral therapy.

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Adult neurogenic deficits in HIV-1 Tg26 transgenic mice

Cited by 27 publications

References 82 publications

Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections

Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections

Oxygen Levels Affect Macrophage HIV-1 Gene Expression and Delay Resolution of Inflammation in HIV-Tg Mice

7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder

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