scholarly journals Functional analysis of Host proteins involved in RNA virus replication

Uirusu ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 71-78
Author(s):  
Seiya YAMAYOSHI
Keyword(s):  
Functional Analysis ◽  
Virus Replication ◽  
Rna Virus ◽  
Host Proteins

scholarly journals RNA-protein interaction analysis of SARS-CoV-2 5’- and 3’-untranslated regions identifies an antiviral role of lysosome-associated membrane protein-2

2021 ◽  
Author(s):  
Rohit Verma ◽  
Sandhini Saha ◽  
Shiv Kumar ◽  
Shailendra Mani ◽  
Tushar Kanti Maiti ◽  
...  
Keyword(s):  
Virus Replication ◽  
Protein Interaction ◽  
Rna Virus ◽  
Protein Interaction Data ◽  
Host Proteins ◽  
Positive Strand ◽  
Protein Protein Interaction ◽  
Infected Cells ◽  
Positive Strand Rna ◽  
Antiviral Role

AbstractSevere acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a positive-strand RNA virus. Viral genome is capped at the 5’-end, followed by an untranslated region (UTR). There is poly-A tail at 3’-end, preceded by an UTR. Self-interaction between the RNA regulatory elements present within 5’- and 3’-UTRs as well as their interaction with host/virus-encoded proteins mediate the function of 5’- and 3’-UTRs. Using RNA-protein interaction detection (RaPID) assay coupled to liquid chromatography with tandem mass-spectrometry, we identified host interaction partners of SARS-CoV-2 5’- and 3’-UTRs and generated an RNA-protein interaction network. By combining these data with the previously known protein-protein interaction data proposed to be involved in virus replication, we generated the RNA-protein-protein interaction (RPPI) network, likely to be essential for controlling SARS-CoV-2 replication. Notably, bioinformatics analysis of the RPPI network revealed the enrichment of factors involved in translation initiation and RNA metabolism. Lysosome-associated membrane protein-2a (Lamp2a) was one of the host proteins that interact with the 5’-UTR. Further studies showed that Lamp2 level is upregulated in SARS-CoV-2 infected cells and overexpression of Lamp2a and Lamp2b variants reduced viral RNA level in infected cells and vice versa. In summary, our study provides an useful resource of SARS-CoV-2 5’- and 3’-UTR binding proteins and reveal the antiviral function of host Lamp2 protein.ImportanceReplication of a positive-strand RNA virus involves an RNA-protein complex consisting of viral genomic RNA, host RNA(s), virus-encoded proteins and host proteins. Dissecting out individual components of the replication complex will help decode the mechanism of viral replication. 5’- and 3’-UTRs in positive-strand RNA viruses play essential regulatory roles in virus replication. Here, we identified the host proteins that associate with the UTRs of SARS-CoV-2, combined those data with the previously known protein-protein interaction data (expected to be involved in virus replication) and generated the RNA-protein-protein interaction (RPPI) network. Analysis of the RPPI network revealed the enrichment of factors involved in translation initiation and RNA metabolism, which are important for virus replication. Analysis of one of the interaction partners of the 5’-UTR (Lamp2a) demonstrated its antiviral role in SARS-CoV-2 infected cells. Collectively, our study provides a resource of SARS-CoV-2 UTR-binding proteins and identifies an antiviral role of host Lamp2a protein.

scholarly journals An inhibitory function of WW domain-containing host proteins in RNA virus replication

Virology ◽  
2012 ◽  
Vol 426 (2) ◽  
pp. 106-119 ◽  
Author(s):  
Jun Qin ◽  
Daniel Barajas ◽  
Peter D. Nagy
Keyword(s):  
Virus Replication ◽  
Rna Virus ◽  
Host Proteins ◽  
Ww Domain ◽  
Inhibitory Function

scholarly journals Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

2020 ◽  
Vol 22 (1) ◽  
pp. 323
Author(s):  
Ramesh Kumar ◽  
Divya Mehta ◽  
Nimisha Mishra ◽  
Debasis Nayak ◽  
Sujatha Sunil
Keyword(s):  
Rna Virus ◽  
Viral Proteins ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Viral Protein Synthesis ◽  
Post Translational Modifications ◽  
Small Proteins ◽  
Cellular Machinery ◽  
Chemical Groups

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

scholarly journals Network-Guided Discovery of Influenza Virus Replication Host Factors

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Emily E. Ackerman ◽  
Eiryo Kawakami ◽  
Manami Katoh ◽  
Tokiko Watanabe ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Replication ◽  
Virus Replication ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Viral Proteins ◽  
Host Factors ◽  
Ppi Network ◽  
Host Proteins ◽  
Influenza Virus Replication

ABSTRACTThe positions of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of virus-regulated pathways (where proteins do not interact with viral proteins), or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining human PPI networks with virus-host PPI data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow, even after the removal of known abundance-degree bias within PPI data. We have isolated a subnetwork of the human PPI network that connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes distinct from those associated with virus-interacting proteins. Selecting proteins based on subnetwork topology, we performed an siRNA screen to determine whether the subnetwork was enriched for virus replication host factors and whether network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins—more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

scholarly journals RNA-Protein Interaction Analysis of SARS-CoV-2 5′ and 3′ Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection

mSystems ◽  
2021 ◽  
Author(s):  
Rohit Verma ◽  
Sandhini Saha ◽  
Shiv Kumar ◽  
Shailendra Mani ◽  
Tushar Kanti Maiti ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Rna Virus ◽  
Untranslated Regions ◽  
Host Proteins ◽  
Positive Strand ◽  
Replication Complex ◽  
Positive Strand Rna Virus ◽  
Positive Strand Rna ◽  
Viral Genomic Rna

Replication of a positive-strand RNA virus involves an RNA-protein complex consisting of viral genomic RNA, host RNA(s), virus-encoded proteins, and host proteins. Dissecting out individual components of the replication complex will help decode the mechanism of viral replication. 5′ and 3′ UTRs in positive-strand RNA viruses play essential regulatory roles in virus replication.

scholarly journals Formation of plant RNA virus replication complexes on membranes: role of an endoplasmic reticulum-targeted viral protein

1997 ◽  
Vol 16 (13) ◽  
pp. 4049-4059 ◽  
Author(s):  
Mary C. Schaad ◽  
Patricia E. Jensen ◽  
James C. Carrington
Keyword(s):  
Endoplasmic Reticulum ◽  
Virus Replication ◽  
Viral Protein ◽  
Rna Virus

scholarly journals Structure–functional analysis of human immunodeficiency virus type 1 (HIV-1) Vpr: role of leucine residues on Vpr-mediated transactivation and virus replication

Virology ◽  
2004 ◽  
Vol 328 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Dineshkumar Thotala ◽  
Elizabeth A. Schafer ◽  
Biswanath Majumder ◽  
Michelle L. Janket ◽  
Marc Wagner ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Human Immunodeficiency Virus ◽  
Virus Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Hiv 1
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