Cocaine-mediated impact on HIV infection in humanized BLT mice

Kim, Sohn G.; Lowe, Emily; Dixit, Dhaval; Youn, Cindy; Kim, Irene J.; Jung, James; Rovner, Robert; Zack, Jerome A.; Vatakis, Dimitrios N.

doi:10.1038/srep10010

Cited by 18 publications

(16 citation statements)

References 55 publications

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“…In vivo studies on the interactions between cocaine and HIV-1 under physiologic conditions have been conducted in a human-mouse hybrid model (huPBL-SCID mouse; Roth et al, 2002 , 2005 ; Kim et al, 2015 ). In this model, cocaine administration led to enhanced HIV-1 infection and a significant rise in circulating virus load ( Roth et al, 2002 , 2005 ; Kim et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of cocaine abuse on HIV pathogenesis

et al. 2015

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Over 1.2 million people in the United States are infected with the human immunodeficiency virus type 1 (HIV-1). Tremendous progress has been made over the past three decades on many fronts in the prevention and treatment of HIV-1 disease. However, HIV-1 infection is incurable and antiretroviral drugs continue to remain the only effective treatment option for HIV infected patients. Unfortunately, only three out of ten HIV-1 infected individuals in the US have the virus under control. Thus, majority of HIV-1 infected individuals in the US are either unaware of their infection status or not connected/retained to care or are non-adherent to antiretroviral therapy (ART). This national public health crisis, as well as the ongoing global HIV/AIDS pandemic, is further exacerbated by substance abuse, which serves as a powerful cofactor at every stage of HIV/AIDS including transmission, diagnosis, pathogenesis, and treatment. Clinical studies indicate that substance abuse may increase viral load, accelerate disease progression and worsen AIDS-related mortality even among ART-adherent patients. However, confirming a direct causal link between substance abuse and HIV/AIDS in human patients remains a highly challenging endeavor. In this review we will discuss the recent and past developments in clinical and basic science research on the effects of cocaine abuse on HIV-1 pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Impact of cocaine abuse on HIV pathogenesis

et al. 2015

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“…In vivo studies in a humanized mouse model revealed that cocaine significantly enhanced HIV-1 infection and increased the circulating viral load1719. Several in vitro studies have demonstrated enhanced HIV-1 infection and replication in T-cells and monocyte-macrophages in the presence of cocaine1314152021.…”

mentioning

confidence: 99%

Cocaine Enhances DC to T-cell HIV-1 Transmission by Activating DC-SIGN/LARG/LSP1 Complex and Facilitating Infectious Synapse Formation

Kulkarni

Jiang

Groopman

2017

Sci Rep

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DC-SIGN is a dendritic cell surface structure which participates in binding and transmission of HIV-1. Here, for the first time we demonstrate that cocaine induces over expression of DC-SIGN and significantly enhances virus transfer from DCs to T-cells by increasing the binding and internalization of HIV-1 in DCs. We found that cocaine activates a DC-SIGN mediated ‘signalosome’ complex by enhancing its association with LARG and LSP1. Further, LARG was observed to participate in DC-SIGN mediated internalization of HIV-1 in DCs. Intracellular trafficking studies of HIV-1 in cocaine treated DCs revealed increased co-localization of HIV-1 with endosomal or multi vesicular body (MVB) markers such as CD81 and VPS4 and decreased co-localization with the phagolysomal marker LAMP1; this signified altered intracellular trafficking and decreased degradation of HIV-1 in cocaine treated DCs. Furthermore, we found that cocaine induced activation of LARG which in turn activated Rho A and the focal adhesion molecules FAK, Pyk2 and paxillin. This signaling cascade enhanced the formation of an infectious synapse between DCs and T-cells. Our study provides insight into the molecular mechanisms of cocaine’s contribution to key components in HIV pathogenesis and highlights novel targets for interrupting the virus life cycle in substance using hosts.

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“…Both cocaine and HIV target the CNS. Besides promoting HIV replication, cocaine primes the cells to become more susceptible for HIV infection [31–33]. Within a few days of infection, HIV establishes a reservoir in the CNS by infecting different types of brain cells including resident microglial cells and astrocytes, along with visiting macrophages, and lymphocytes [31, 32, 34–37].…”

Section: Cns Is the Common Target For Cocaine And Hivmentioning

confidence: 99%

“…Thus, illicit drug using HIV patients are more prone to the HIV associated comorbidities. Furthermore, the direct correlation of cocaine use with enhanced HIV replications has been well documented by several investigations using HIV infected humanized mouse models [32, 33, 49]. Hence, drug addiction extraordinarily contributes to the health and financial burden on HIV patients and the society as a whole [5, 6].…”

Section: Cns Is the Common Target For Cocaine And Hivmentioning

confidence: 99%

The effects of cocaine on HIV transcription

et al. 2015

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Illicit drug users are a high risk population for infection with the Human Immunodeficiency Virus (HIV). A strong correlation exists between prohibited drugs use and an increase rate of HIV transmission. Cocaine stands out as one of the most frequently abused illicit drugs and its use is correlated with HIV infection and disease progression. The central nervous system (CNS) is a common target for both drugs of abuse and HIV, and cocaine intake further accelerates neuronal injury in HIV patients. Although the high incidence of HIV infection in illicit drug abusers is primarily due to high risk activities such as needle sharing and unprotected sex, several studies have demonstrated that cocaine enhances the rate of HIV gene expression and replication by activating various signal transduction pathways and downstream transcription factors. In order to generate mature HIV genomic transcript, HIV gene expression has to pass through both the initiation and elongation phases of transcription, which requires discrete transcription factors. In this review, we will provide a detailed analysis of the molecular mechanisms that regulate HIV transcription and discuss how cocaine modulates those mechanisms to upregulate HIV transcription and eventually HIV replication.

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Cocaine-mediated impact on HIV infection in humanized BLT mice

Cited by 18 publications

References 55 publications

Impact of cocaine abuse on HIV pathogenesis

Impact of cocaine abuse on HIV pathogenesis

Cocaine Enhances DC to T-cell HIV-1 Transmission by Activating DC-SIGN/LARG/LSP1 Complex and Facilitating Infectious Synapse Formation

The effects of cocaine on HIV transcription

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