Macrophages and HIV-1: dangerous liaisons

Verani, Alessia; Gras, Gabriel; Pancino, Gianfranco

doi:10.1016/j.molimm.2004.06.020

Cited by 100 publications

(79 citation statements)

References 229 publications

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“…HAD describes the cognitive deficits, motor disturbances, and behavioral abnormalities often observed in HIV-infected individuals (for reviews see (Kaul et al 2001;McArthur et al 2003;Gonzalez-Scarano and Martin-Garcia 2005;Kramer-Hammerle et al 2005;Verani et al 2005)). Although the incidence of HAD has decreased from an estimated 30% to ~10% in the era of HAART, it remains a significant complication of HIV-1 infection as patients with acquired immunodeficiency syndrome (AIDS) live longer, antiretroviral drugs remain unable to effectively cross the blood brain barrier, and HIV-1 resistance grows due to viral strain mutation.…”

Section: Introductionmentioning

confidence: 99%

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Keblesh

Xiong

2008

J Neuroimmune Pharmacol

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Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD), a severe form of HIV-associated neurocognitive disorders (HAND), describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (brain perivascular macrophages and microglia) releasing immune and viral products in the brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates voltage-gated potassium (K v ) channels, key regulators of cell excitability and animal behavior (learning and memory), are involved in the pathogenesis of HAD/HAND. Here we survey the literature and find that HAD-related alterations in cellular and viral products can increase neuronal K v channel activity, leading to neuronal dysfunction and cognitive deficits. Thus, neuronal K v channels may be a new target in the effort to develop therapies for HAD and perhaps other inflammatory neurodegenerative disorders.

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Section: Introductionmentioning

confidence: 99%

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Keblesh

Xiong

2008

J Neuroimmune Pharmacol

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“…HIV-1 infection results from the actions of viral proteins, including the envelope glycoprotein 120 (gp120), on targeted cells, such as macrophages and Tlymphocytes [44][45][46][47][48][49] . HAART suppresses the growth of HIV-1 but does not eliminate HIV-1 infection [10][11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Role of HIV-1 Infection in Addictive Behavior: A Study of a HIV-1 Transgenic Rat Model

Chang¹,

Vigorito²

2006

American J. of Infectious Diseases

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Epidemiological research indicates that drug abuse is prevalent among individuals infected with HIV-1. Evidence from preclinical research also suggests that drugs of abuse exacerbate the progression of neuropathological changes in the HIV-1 infected brain probably through common mechanisms of neuronal injury. The effects of HIV-1 on the efficacy and abuse potential of controlled drugs such as morphine, however, has not been explored. The current study reports that the noninfectious HIV-1 transgenic (HIV-1 Tg) rat shows up-regulated expression of the mu opioid receptor (MOR) at the transcriptional level and functional supersensitivity to morphine, a MOR agonist. Compared to nontransgenic control rats, the HIV-1 Tg rats also show greater motivation to run in a wheel, a behavior that is known to be associated with increased drug self-administration. These results suggest the potential role of HIV-1 infection in enhancing vulnerability to addiction and this possibility warrants further investigation to better understand the link between HIV-1 infection and the abuse of drugs including opioids.

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“…M acrophage infection by HIV-1 contributes to viral pathogenesis and progression to AIDS (1). Because of their longevity and relative resistance to the cytopathogenic effect of HIV-1, macrophages contribute to the establishment of viral reservoirs and are able to transmit the virus to other target cells (2)(3)(4).…”

mentioning

confidence: 99%

p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway

Allouch

David

Amie

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Macrophages are a major target cell for HIV-1, and their infection contributes to HIV pathogenesis. We have previously shown that the cyclin-dependent kinase inhibitor p21 inhibits the replication of HIV-1 and other primate lentiviruses in human monocyte-derived macrophages by impairing reverse transcription of the viral genome. In the attempt to understand the p21-mediated restriction mechanisms, we found that p21 impairs HIV-1 and simian immunodeficiency virus (SIV)mac reverse transcription in macrophages by reducing the intracellular deoxyribonucleotide (dNTP) pool to levels below those required for viral cDNA synthesis by a SAM domain and HD domain-containing protein 1 (SAMHD1)-independent pathway. We found that p21 blocks dNTP biosynthesis by down-regulating the expression of the RNR2 subunit of ribonucleotide reductase, an enzyme essential for the reduction of ribonucleotides to dNTP. p21 inhibits RNR2 transcription by repressing E2F1 transcription factor, its transcriptional activator. Our findings unravel a cellular pathway that restricts HIV-1 and other primate lentiviruses by affecting dNTP synthesis, thereby pointing to new potential cellular targets for anti-HIV therapeutic strategies.

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Macrophages and HIV-1: dangerous liaisons

Cited by 100 publications

References 229 publications

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Role of HIV-1 Infection in Addictive Behavior: A Study of a HIV-1 Transgenic Rat Model

p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway

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