HIV Subtypes B and C gp120 and Methamphetamine Interaction

Dopaminergic System Implicates Differential Neuronal Toxicity

Thangavel Samikkannu, Kurapati V.K. Rao, Abdul Ajees Abdul Salam, Venkata S.R. Atluri, Elena M. Kaftanovskaya, Marisela Agudelo, Suray Perez, Changwon Yoo, Andrea D. Raymond, Hong Ding, Madhavan P.N. Nair

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.

Original languageEnglish
Article number11130
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 09-06-2015

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Methamphetamine
HIV
HIV-1
Dopamine Agents
Astrocytes
Substance-Related Disorders
Disease Progression
Central Nervous System
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Samikkannu, T., Rao, K. V. K., Salam, A. A. A., Atluri, V. S. R., Kaftanovskaya, E. M., Agudelo, M., ... Nair, M. P. N. (2015). HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity. Scientific Reports, 5, [11130]. https://doi.org/10.1038/srep11130
Samikkannu, Thangavel ; Rao, Kurapati V.K. ; Salam, Abdul Ajees Abdul ; Atluri, Venkata S.R. ; Kaftanovskaya, Elena M. ; Agudelo, Marisela ; Perez, Suray ; Yoo, Changwon ; Raymond, Andrea D. ; Ding, Hong ; Nair, Madhavan P.N. / HIV Subtypes B and C gp120 and Methamphetamine Interaction : Dopaminergic System Implicates Differential Neuronal Toxicity. In: Scientific Reports. 2015 ; Vol. 5.
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abstract = "HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.",
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Samikkannu, T, Rao, KVK, Salam, AAA, Atluri, VSR, Kaftanovskaya, EM, Agudelo, M, Perez, S, Yoo, C, Raymond, AD, Ding, H & Nair, MPN 2015, 'HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity', Scientific Reports, vol. 5, 11130. https://doi.org/10.1038/srep11130

HIV Subtypes B and C gp120 and Methamphetamine Interaction : Dopaminergic System Implicates Differential Neuronal Toxicity. / Samikkannu, Thangavel; Rao, Kurapati V.K.; Salam, Abdul Ajees Abdul; Atluri, Venkata S.R.; Kaftanovskaya, Elena M.; Agudelo, Marisela; Perez, Suray; Yoo, Changwon; Raymond, Andrea D.; Ding, Hong; Nair, Madhavan P.N.

In: Scientific Reports, Vol. 5, 11130, 09.06.2015.

Research output: Contribution to journalArticle

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T2 - Dopaminergic System Implicates Differential Neuronal Toxicity

AU - Samikkannu, Thangavel

AU - Rao, Kurapati V.K.

AU - Salam, Abdul Ajees Abdul

AU - Atluri, Venkata S.R.

AU - Kaftanovskaya, Elena M.

AU - Agudelo, Marisela

AU - Perez, Suray

AU - Yoo, Changwon

AU - Raymond, Andrea D.

AU - Ding, Hong

AU - Nair, Madhavan P.N.

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N2 - HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.

AB - HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.

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