Retrovirus Entry by Endocytosis and Cathepsin Proteases

Kubo, Yasuo; Hayashi, Hideki; Matsuyama, Tomohiro; Sato, Hironori; Yamamoto, Naoki

doi:10.1155/2012/640894

Cited by 27 publications

(26 citation statements)

References 136 publications

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“…2a and Additional file 10). Cathepsins are proteases involved in many biological processes, including protein degradation, apoptosis, and signaling, and their activity in the late endosome and lysosome has been widely implicated in virus transmission [35, 36]. A total of 111 cathepsin genes were detected in the B. tabaci genome (Fig.…”

Section: Resultsmentioning

confidence: 99%

The draft genome of whitefly Bemisia tabaci MEAM1, a global crop pest, provides novel insights into virus transmission, host adaptation, and insecticide resistance

et al. 2016

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BackgroundThe whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is among the 100 worst invasive species in the world. As one of the most important crop pests and virus vectors, B. tabaci causes substantial crop losses and poses a serious threat to global food security.ResultsWe report the 615-Mb high-quality genome sequence of B. tabaci Middle East-Asia Minor 1 (MEAM1), the first genome sequence in the Aleyrodidae family, which contains 15,664 protein-coding genes. The B. tabaci genome is highly divergent from other sequenced hemipteran genomes, sharing no detectable synteny. A number of known detoxification gene families, including cytochrome P450s and UDP-glucuronosyltransferases, are significantly expanded in B. tabaci. Other expanded gene families, including cathepsins, large clusters of tandemly duplicated B. tabaci-specific genes, and phosphatidylethanolamine-binding proteins (PEBPs), were found to be associated with virus acquisition and transmission and/or insecticide resistance, likely contributing to the global invasiveness and efficient virus transmission capacity of B. tabaci. The presence of 142 horizontally transferred genes from bacteria or fungi in the B. tabaci genome, including genes encoding hopanoid/sterol synthesis and xenobiotic detoxification enzymes that are not present in other insects, offers novel insights into the unique biological adaptations of this insect such as polyphagy and insecticide resistance. Interestingly, two adjacent bacterial pantothenate biosynthesis genes, panB and panC, have been co-transferred into B. tabaci and fused into a single gene that has acquired introns during its evolution.ConclusionsThe B. tabaci genome contains numerous genetic novelties, including expansions in gene families associated with insecticide resistance, detoxification and virus transmission, as well as numerous horizontally transferred genes from bacteria and fungi. We believe these novelties likely have shaped B. tabaci as a highly invasive polyphagous crop pest and efficient vector of plant viruses. The genome serves as a reference for resolving the B. tabaci cryptic species complex, understanding fundamental biological novelties, and providing valuable genetic information to assist the development of novel strategies for controlling whiteflies and the viruses they transmit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0321-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

The draft genome of whitefly Bemisia tabaci MEAM1, a global crop pest, provides novel insights into virus transmission, host adaptation, and insecticide resistance

et al. 2016

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“…While CD4-independent cell entry occur through acidic endosomes and is inhibited by cathepsin B [42]. As reviewed [43], these findings suggest that HIV-1 may have developed an acidification-independent entry mechanism to overcome cathepsin B digestion in late endosome. Lysosomal permeabilization has also been linked with HIV replication, as diffusion of cathepsins B, L and D into the cytosol is enhanced when CD4+ lymphocytes are infected with HIV-1, and inhibited by addition of 2′,3′-dideoxyinosine (didanosine or ddI), an HIV reverse transcriptase inhibitor [44].…”

Section: Macrophage Derived Cystatin B/cathepsin B In Hiv Replicamentioning

confidence: 99%

Macrophage Derived Cystatin B/Cathepsin B in HIV Replication and Neuropathogenesis

Rivera¹,

Colón²,

Cantres-Rosario³

et al. 2014

CHR

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Mononuclear phagocytes including monocytes and macrophages, are important defense components of innate immunity, but can be detrimental in HIV-1 infection by serving as the principal reservoirs of virus in brain and triggering a strong immune response. These viral reservoirs represent a challenge to HIV-1 eradication since they continue producing virus in tissue despite antiretroviral therapy. HIV-1 associated neurocognitive disorders (HAND) involve alterations to the blood-brain barrier and migration of activated HIV-1 infected monocytes to the brain with subsequent induced immune activation response. Our group recently showed that HIV replication in monocyte-derived macrophages is associated with increased cystatin B. This cysteine protease inhibitor also inhibits the interferon-induced antiviral response by decreasing levels of tyrosine phosphorylated STAT-1. These recent discoveries reveal novel mechanisms of HIV persistence that could be targeted by new therapeutic approaches to eliminate HIV in macrophage reservoirs. However, cystatin B has been also associated with neuroprotection. Cystatin B is an inhibitor of the cysteine protease cathepsin B, a potent neurotoxin. During HIV-1 infection cystatin B and cathepsin B are upregulated in macrophages. Reduction in cystatin/cathepsin interactions in infected macrophages leads to increased cathepsin B secretion and activity which contributes to neuronal apoptosis. Increased intracellular expression of both proteins was recently found in monocytes from Hispanic women with HAND. These findings provide new evidence for the role of cathepsin /cystatin system in the neuropathogenesis induced by HIV-infected macrophages. We summarize recent research on cystatin B and one of its substrates, cathepsin B, in HIV replication in macrophages and neuropathogenesis.

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“…The viral particle can also enter the cell by endocytosis (41). Many viruses, including retroviruses such as HIV-1, use endocytosis as an entry route (41,42) although several other factors can enhance viral entry in this circumstance (43).…”

Section: Discussionmentioning

confidence: 99%

JAK-STAT Signaling Pathways and Inhibitors Affect Reversion of Envelope-Mutated HIV-1

Quan

Han

et al. 2017

J Virol

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HIV can spread by both cell-free and cell-to-cell transmission. Here, we show that many of the amino acid changes in Env that are close to the CD4 binding pocket can affect HIV replication. We generated a number of mutant viruses that were unable to infect T cells as cell-free viruses but were nevertheless able to infect certain T cell lines as cell-associated viruses, which was followed by reversion to the wild type. However, the activation of JAK-STAT signaling pathways caused the inhibition of such cell-to-cell infection as well as the reversion of multiple HIV Env mutants that displayed differences in their abilities to bind to the CD4 receptor. Specifically, two T cell activators, interleukin-2 (IL-2) and phorbol 12-myristate 13-acetate (PMA), both capable of activation of JAK-STAT pathways, were able to inhibit cell-tocell viral transmission. In contrast, but consistent with the above result, a number of JAK-STAT and mTOR inhibitors actually promoted HIV-1 transmission and reversion. Hence, JAK-STAT signaling pathways may differentially affect the replication of a variety of HIV Env mutants in ways that differ from the role that these pathways play in the replication of wild-type viruses.IMPORTANCE Specific alterations in HIV Env close to the CD4 binding site can differentially change the ability of HIV to mediate infection for cell-free and cell-associated viruses. However, such differences are dependent to some extent on the types of target cells used. JAK-STAT signaling pathways are able to play major roles in these processes. This work sheds new light on factors that can govern HIV infection of target cells.KEYWORDS HIV-1, Env mutant, cell-associated viruses, cell dependence, reversion H IV-1 infection of cells can be efficiently established by free virus or directly via cell-cell contact, both involving the binding of the HIV gp120 protein to the cellular CD4 receptor and either the CCR5 or CXCR4 coreceptor (1-3). It has been reported that cell-to-cell transmission is more physiologically relevant and efficient although cell-free HIV may be used to initiate new infections in tissue culture (4-7).HIV-1 entry into target cells is believed to be a multistep and complex process initiated by the envelope protein gp120 binding to cell surface CD4, triggering conformational changes of gp120, followed by a second-step interaction between gp120 and either CXCR4 or CCR5, resulting in fusion between the viral envelope and the cellular plasma membrane (8). In addition to viral gp120 and other viral proteins, several host cell components, including intrinsic immune factors (9) and histocompatibility antigens, can influence HIV infectivity (10, 11). However, some viral factors can also counteract innate host defense mechanisms (12). It has also been reported that HIV can under some circumstances enter target cells via a CD4/coreceptor-independent mechanism (13-18), potentially broadening the spectrum of cells that HIV is able to infect.

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Retrovirus Entry by Endocytosis and Cathepsin Proteases

Cited by 27 publications

References 136 publications

The draft genome of whitefly Bemisia tabaci MEAM1, a global crop pest, provides novel insights into virus transmission, host adaptation, and insecticide resistance

The draft genome of whitefly Bemisia tabaci MEAM1, a global crop pest, provides novel insights into virus transmission, host adaptation, and insecticide resistance

Macrophage Derived Cystatin B/Cathepsin B in HIV Replication and Neuropathogenesis

JAK-STAT Signaling Pathways and Inhibitors Affect Reversion of Envelope-Mutated HIV-1

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