HIV-1 Nef Inhibits Lipopolysaccharide-induced IL-12p40 Expression by Inhibiting JNK-activated NFκB in Human Monocytic Cells

Ma, Wei; Mishra, Sasmita; Gajanayaka, Niranjala; Angel, Jonathan B.; Kumar, Ashok

doi:10.1074/jbc.m710013200

Cited by 9 publications

(2 citation statements)

References 71 publications

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“…Interleukins are a group of cytokines and its large portions are responsible for the development of human immune system. Poor production of Th1-type cytokines including interleukin-12 (IL-12) is generally observed in CD4+T cells during the acute immunodeficiency syndrome associated with HIV-1 progression [ 36 ]. Cellular immunity is critically depended on Interleukins and its production is significantly decreased during HIV infection.…”

Section: Resultsmentioning

confidence: 99%

Incorporating the type and direction information in predicting novel regulatory interactions between HIV-1 and human proteins using a biclustering approach

2014

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BackgroundDiscovering novel interactions between HIV-1 and human proteins would greatly contribute to different areas of HIV research. Identification of such interactions leads to a greater insight into drug target prediction. Some recent studies have been conducted for computational prediction of new interactions based on the experimentally validated information stored in a HIV-1-human protein-protein interaction database. However, these techniques do not predict any regulatory mechanism between HIV-1 and human proteins by considering interaction types and direction of regulation of interactions.ResultsHere we present an association rule mining technique based on biclustering for discovering a set of rules among human and HIV-1 proteins using the publicly available HIV-1-human PPI database. These rules are subsequently utilized to predict some novel interactions among HIV-1 and human proteins. For prediction purpose both the interaction types and direction of regulation of interactions, (i.e., virus-to-host or host-to-virus) are considered here to provide important additional information about the regulation pattern of interactions. We have also studied the biclusters and analyzed the significant GO terms and KEGG pathways in which the human proteins of the biclusters participate. Moreover the predicted rules have also been analyzed to discover regulatory relationship between some human proteins in course of HIV-1 infection. Some experimental evidences of our predicted interactions have been found by searching the recent literatures in PUBMED. We have also highlighted some human proteins that are likely to act against the HIV-1 attack.ConclusionsWe pose the problem of identifying new regulatory interactions between HIV-1 and human proteins based on the existing PPI database as an association rule mining problem based on biclustering algorithm. We discover some novel regulatory interactions between HIV-1 and human proteins. Significant number of predicted interactions has been found to be supported by recent literature.

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Section: Resultsmentioning

confidence: 99%

Incorporating the type and direction information in predicting novel regulatory interactions between HIV-1 and human proteins using a biclustering approach

2014

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“…It has been reported that INT interacts with INI1 [24], and concerted action of JNK and Pin1 increases INT stability, which is required for efficient HIV-1 integration and infection [13]. Since Nef activates JNK [49–53], which phosphorylates INT [13], and since our data indicate that infection with HSIVnef, but not HIV-1, results in efficient integration of proviral DNA into the host genome in resting hPBMCs (Fig. 4), the corresponding N-terminal fragment of SIVpbj1.9 Nef in HIV-1 is sufficient to increase INT stability by activating JNK.…”

Section: Discussionmentioning

confidence: 99%

Interaction between Nef and INI1/SMARCB1 augments replicability of HIV-1 in resting human peripheral blood mononuclear cells

Pyeon

Park

2015

Arch Virol

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A central feature of HIV-1 infection is the inability of entering virus to integrate into chromosomes of resting T lymphocytes unless they are mitogenically activated. In contrast, SIVpbj1.9 replicates in initially resting T lymphocytes by activating infected cells. Previous reports have shown that a difference in Nef-mediated T cell activation between HIV-1 and SIVpbj1.9 plays a critical role in the differing abilities of these viruses to replicate in resting lymphocytes. However, the molecular details of these differences are still unclear. Here, we show that infection with a chimeric virus, HSIVnef, which harbors the 5′ 308 nucleotides of SIVpbj1.9 nef in place of the 5′ 221 nucleotides of HIV-1 nef in the HIV-1 proviral backbone, resulted in integration of the provirus into host chromosomes without mitogenic activation and thereby replication in resting human PBMCs (hPBMCs). These results indicate that Nef is an essential viral determinant for the integration of provirus into host chromosomes in resting T cells. Using the yeast two-hybrid system, we identified integrase interactor-1 (INI1/SMARCB1) as a cellular factor that is involved in the integration process via interaction with Nef. Although INI1 interacted with both SIVpbj1.9 and HIV-1 Nefs, SIVpbj1.9 Nef, but not HIV-1 Nef, enhanced proviral integration into host DNA. Furthermore, mutational analysis revealed that the basic-amino-acid-rich amino-terminal domain in SIVpbj1.9 Nef is crucial for interaction with INI1 and virus replication in resting hPBMCs. Taken together, these data indicate that Nef is a critical viral protein for incorporating nascent proviral DNA into host chromosomes in resting PBMCs and that this occurs through interaction with INI1. This elucidates the basis for replication of the integrated provirus when the host cell is in a resting state.

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Programmed death-1 receptor negatively regulates LPS-mediated IL-12 production and differentiation of murine macrophage RAW264.7 cells

et al. 2009

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HIV-1 Nef Inhibits Lipopolysaccharide-induced IL-12p40 Expression by Inhibiting JNK-activated NFκB in Human Monocytic Cells

Cited by 9 publications

References 71 publications

Incorporating the type and direction information in predicting novel regulatory interactions between HIV-1 and human proteins using a biclustering approach

Incorporating the type and direction information in predicting novel regulatory interactions between HIV-1 and human proteins using a biclustering approach

Interaction between Nef and INI1/SMARCB1 augments replicability of HIV-1 in resting human peripheral blood mononuclear cells

Programmed death-1 receptor negatively regulates LPS-mediated IL-12 production and differentiation of murine macrophage RAW264.7 cells

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