Induction of HIV Transcription by Nef Involves Lck Activation and Protein Kinase Cθ Raft Recruitment Leading to Activation of ERK1/2 but Not NFκB

Witte, Vanessa; Laffert, Bernd; Gintschel, Patricia; Krautkrämer, Ellen; Blume, Katja; Fackler, Oliver T.; Baur, Andreas S.

doi:10.4049/jimmunol.181.12.8425

Cited by 34 publications

(31 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that although GP120 signals primarily through CXCR4, CD4 or other molecules may also be needed [28]. The CD4-associated kinase Lck has recently ( 70,71 ) GP120 GP120 been linked to P38 activation [30]. In the past few years, it has been shown that P38a can also be activated through an ''alternative pathway'' in T cells [30].…”

Section: Hiv Infection and P38 Signalingmentioning

confidence: 96%

See 1 more Smart Citation

Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response

Furler

Uíttenbogaart

2010

Immunol Res

View full text Add to dashboard Cite

One of the defining characteristics of HIV is its ability to manipulate the human immune response to promote its own replication. Since the beginning of the epidemic, there has been controversy whether a robust immune response to the virus is beneficial or detrimental for the host. Therefore, the effects of HIV on signaling pathways and cytokine production need to be characterized in order to distinguish between protective immune responses and inappropriate immune activation. Cytokine and biomarker expression during HIV infection results from the combined effects of intracellular signaling pathways orchestrated by kinases like P38 and ERK. The P38 and ERK Mitogen-Activated Protein Kinase (MAPK) pathways govern the regulation of cytokines (IL-2, IL-10, and TNF-α) as well biomarkers (PD-1, Fas/FasL, among others) that are skewed in chronic HIV infection. HIV utilizes the P38 and ERK pathways to produce new virions and to deplete CD4+ T cells from the host's immune system. Understanding the interplay between HIV and the cytokines induced by activation of the P38 and ERK pathways may provide insights into HIV immunopathogenesis and the development of a protective vaccine.

show abstract

Section: Hiv Infection and P38 Signalingmentioning

confidence: 96%

“…Witte et al [70] found that HIV Nef can induce ERK1/2 signaling through Lck and PKCh recruitment to lipid rafts. Schrager et al [71] also showed that HIV Nef increased ERK activity in primary CD4 T cells.…”

Section: Hiv Infection and Erk Signalingmentioning

confidence: 98%

Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response

Furler

Uíttenbogaart

2010

Immunol Res

View full text Add to dashboard Cite

show abstract

“…Note that hnRNP-K plays essential roles in transcriptional processes and molecular interactions (227). Overall, Nef exerts an impact on Tat-mediated transcription either by direct interaction or by signaling pathways mediated via cellular cofactors (223)(224)(225)(226). The exact protein domains that mediate the Tat-Nef interaction remain unclear.…”

Section: Tat-nef Interactionmentioning

confidence: 99%

“…First, Nef induces many host factors (e.g., CDK9, Tat-SF1, and IRF2) to promote Tat-mediated transcriptional activity (224). Second, Nef-mediated signaling can enhance Tat-mediated transcriptional activity via an extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK)-dependent pathway (225). Third, Nef promotes Tat-mediated transcription via the heterogeneous nuclear ribonucleoprotein K (hnRNP-K)-nucleated signaling complex (226).…”

Section: Tat-nef Interactionmentioning

confidence: 99%

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Clercq

2016

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.

show abstract

“…Though ERK and p38 MAPK signaling molecules can modulate T-cell function [14], these molecules have different effects on T-cell development, cell cycle progression, and apoptosis [23,24,25]. Also, it is significant that the MAPK signaling pathway is known to interact with HIV-1 viral proteins [26]. As shown in figure 2a, cotreatment of SAHA and TPA could induce HIV-1 reactivation via not the p38 MAPK pathway but the ERK pathway in HIV-1 latently infected cells (fig.…”

Section: Tablementioning

confidence: 99%

Histone Deactylase Inhibitor SAHA Induces a Synergistic HIV-1 Reactivation by 12-O-Tetradecanoylphorbol-13-Acetate in Latently Infected Cells

et al. 2013

View full text Add to dashboard Cite

Objectives: Recent studies have reported that human immunodeficiency virus type 1 (HIV-1) proviruses are strongly suppressed in the unique epigenetic environments caused by chromatin modifications such as acetylation and methylation. Therefore, optimized therapeutic strategies directed against the virus reservoir using these epigenetic modifying agents (EMAs) should cure HIV infection. Methods: Cytotoxicity and HIV-1 reactivation were determined using the PrestoBlue™ Cell Viability Reagent and p24 HIV ELISA, respectively. Results: EMAs, including histone deacetylase inhibitors (VPA and SAHA), DNA methyltransferase inhibitor (5′-Aza-CdR), histone methyltransferase inhibitor (ADOX) and 12-O-tetradecanoylphorbol-13-acetate (TPA), were used to reactivate proviruses in HIV-1 latently infected cells. The effect of monotreatment with these EMAs on HIV-1 reactivation was VPA or SAHA > 5′-Aza-CdR > ADOX. Even though cotreatment with these potential HIV-1 reactivating agents did not show any significant reactivation effects in HIV-1 latently infected cells, employing SAHA under TPA treatment demonstrated a dramatic synergistic effect on purging HIV-1 proviruses in all HIV-1 latently infected cells via the ERK and AP-1 pathways. Conclusions: These results suggest that the combined approaches of EMAs, cotreatment of SAHA and TPA, could provide an effective way to lead a decline of HIV-1 reservoirs in patients.

show abstract

Induction of HIV Transcription by Nef Involves Lck Activation and Protein Kinase Cθ Raft Recruitment Leading to Activation of ERK1/2 but Not NFκB

Cited by 34 publications

References 38 publications

Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response

Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Histone Deactylase Inhibitor SAHA Induces a Synergistic HIV-1 Reactivation by 12-O-Tetradecanoylphorbol-13-Acetate in Latently Infected Cells

Contact Info

Product

Resources

About