UPF1 Is Crucial for the Infectivity of Human Immunodeficiency Virus Type 1 Progeny Virions

Serquiña, Anna K. P.; Das, Suman; Попова, Е. Н.; Ojelabi, Ogooluwa; Roy, Christian K.; Göttlinger, Heinrich G.

doi:10.1128/jvi.00925-13

Cited by 47 publications

(48 citation statements)

References 50 publications

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“…In this case, it is likely due to further alteration of nucleic acid configuration, leading to a block in reverse transcription. Our data complements a number of reports showing that the cellular proteins incorporated into the virions from producer cells can significantly alter the infectivity of the virions ((Serquiña et al, 2013), reviewed in Iordanskiy et al (2013)). MCM5 has the properties of an inhibitory factor that limits HIV-1 replication by interfering with production of an integration-competent cDNA product.…”

Section: Discussionsupporting

confidence: 86%

Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells

et al. 2016

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The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. Our data suggest that incorporation of physiological amounts of MCM5 promotes aberrant reverse transcription, leading to partial incapacitation of cDNA, whereas increased MCM5 abundance leads to reduced reverse transcription and infection. Therefore, MCM5 has the properties of an inhibitory factor that interferes with production of an integration-competent cDNA product.

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Section: Discussionsupporting

confidence: 86%

Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells

et al. 2016

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“…UPF1 is well known for its involvement in the NMD pathway (42) and was recently reported to restrict Semliki Forest virus infection. In contrast to restriction of viral replication, UPF1 is required for HIV1 virion production (47). In this study, we found that UPF1 is required for HCV replication (Fig.…”

Section: Discussionmentioning

confidence: 49%

Affinity Purification of the Hepatitis C Virus Replicase Identifies Valosin-Containing Protein, a Member of the ATPases Associated with Diverse Cellular Activities Family, as an Active Virus Replication Modulator

Fang

Zou

et al. 2016

J Virol

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Like almost all of the positive-strand RNA viruses, hepatitis C virus (HCV) induces host intracellular membrane modification to form the membrane-bound viral replication complex (RC), within which viral replicases amplify the viral RNA genome. Despite accumulated information about how HCV co-opts host factors for viral replication, our knowledge of the molecular mechanisms by which viral proteins hijack host factors for replicase assembly has only begun to emerge. Purification of the viral replicase and identification of the replicase-associated host factors to dissect their roles in RC biogenesis will shed light on the molecular mechanisms of RC assembly. To purify the viral replicase in the context of genuine viral replication, we developed an HCV subgenomic replicon system in which two different affinity tags were simultaneously inserted in frame into HCV NS5A and NS5B. After solubilizing the replicon cells, we purified the viral replicase by two-step affinity purification and identified the associated host factors by mass spectrometry. We identified valosin-containing protein (VCP), a member of the ATPases associated with diverse cellular activities (AAA؉ATPase) family, as an active viral replication modulator whose ATPase activity is required for viral replication. A transient replication assay indicated that VCP is involved mainly in viral genome amplification. VCP associated with viral replicase and colocalized with a viral RC marker. Further, in an HCV replicase formation surrogate system, abolishing VCP function resulted in aberrant distribution of HCV NS5A. We propose that HCV may co-opt a host AAA؉ATPase for its replicase assembly. IMPORTANCEAlmost all of the positive-strand RNA viruses share a replication strategy in which viral proteins modify host membranes to form the membrane-associated viral replicase. Viruses hijack host factors to facilitate this energy-unfavorable process. Understanding of this fundamental process is hampered by the challenges of purifying the replicase because of the technical difficulties involved. In this study, we developed an HCV subgenomic replicon system in which two different affinity tags were simultaneously inserted in frame into two replicase components. Using this dual-affinity-tagged replicon system, we purified the viral replicase and identified valosin-containing protein (VCP) AAA؉ATPase as a pivotal viral replicase-associated host factor that is required for viral genome replication. Abolishing VCP function resulted in aberrant viral protein distribution. We propose that HCV hijacks a host AAA؉ATPase for its replicase assembly. Understanding the molecular mechanism of VCP regulates viral replicase assembly may lead to novel antiviral strategies targeting the most conserved viral replication step.T he positive-strand RNA viruses are the largest class of viruses and include many medically and economically important pathogens, including hepatitis C virus (HCV); picornaviruses, which cause hand, foot, and mouth disease; and flaviviruses, such as the West N...

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“…Instead, using Rev‐deficient constructs, the authors recently showed that recruitment of UPF1 to these nuclear retained transcripts promotes their CRM1‐dependent export to the cytoplasm . UPF1 remains associated with HIV‐1 RNA in the cytoplasm and together with other cellular RNA‐binding proteins, UPF1 is packed into the HIV‐1 virions and was shown to be crucial for the infectivity of the virus . Available evidence suggests that UPF1 functions at the step of reverse transcription and that this function requires the helicase activity of UPF1, but the exact mechanism is not yet understood …”

Section: Biological Functions Of Nmdmentioning

confidence: 99%

Nonsense‐mediated mRNA decay: novel mechanistic insights and biological impact

2016

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Nonsense-mediated mRNA decay (NMD) was originally coined to define a quality control mechanism that targets mRNAs with truncated open reading frames due to the presence of a premature termination codon. Meanwhile, it became clear that NMD has a much broader impact on gene expression and additional biological functions beyond quality control are continuously being discovered. We review here the current views regarding the molecular mechanisms of NMD, according to which NMD ensues on mRNAs that fail to terminate translation properly, and point out the gaps in our understanding. We further summarize the recent literature on an ever-rising spectrum of biological processes in which NMD appears to be involved, including homeostatic control of gene expression, development and differentiation, as well as viral defense.

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UPF1 Is Crucial for the Infectivity of Human Immunodeficiency Virus Type 1 Progeny Virions

Cited by 47 publications

References 50 publications

Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells

Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells

Affinity Purification of the Hepatitis C Virus Replicase Identifies Valosin-Containing Protein, a Member of the ATPases Associated with Diverse Cellular Activities Family, as an Active Virus Replication Modulator

Nonsense‐mediated mRNA decay: novel mechanistic insights and biological impact

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