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1.
PLoS Pathog ; 17(10): e1009412, 2021 10.
Article in English | MEDLINE | ID: covidwho-1448584

ABSTRACT

Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.


Subject(s)
COVID-19/metabolism , Host-Parasite Interactions/physiology , SARS-CoV-2/metabolism , Viral Proteins/metabolism , Humans , Protein Biosynthesis/physiology , Proteome/metabolism
2.
Front Immunol ; 12: 638573, 2021.
Article in English | MEDLINE | ID: covidwho-1376694

ABSTRACT

Animal viruses are parasites of animal cells that have characteristics such as heredity and replication. Viruses can be divided into non-enveloped and enveloped viruses if a lipid bilayer membrane surrounds them or not. All the membrane proteins of enveloped viruses that function in attachment to target cells or membrane fusion are modified by glycosylation. Glycosylation is one of the most common post-translational modifications of proteins and plays an important role in many biological behaviors, such as protein folding and stabilization, virus attachment to target cell receptors and inhibition of antibody neutralization. Glycans of the host receptors can also regulate the attachment of the viruses and then influence the virus entry. With the development of glycosylation research technology, the research and development of novel virus vaccines and antiviral drugs based on glycan have received increasing attention. Here, we review the effects of host glycans and viral proteins on biological behaviors of viruses, and the opportunities for prevention and treatment of viral infectious diseases.


Subject(s)
Host-Parasite Interactions/physiology , Polysaccharides/metabolism , Receptors, Virus/metabolism , Virus Internalization , Viruses , Animals , Glycosylation , Humans , Immune Evasion , Viruses/immunology , Viruses/metabolism
3.
mBio ; 12(4): e0121421, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1297963

ABSTRACT

As access to high-throughput sequencing technology has increased, the bottleneck in biomedical research has shifted from data generation to data analysis. Here, we describe a modular and extensible framework for didactic instruction in bioinformatics using publicly available RNA sequencing data sets from infectious disease studies, with a focus on host-parasite interactions. We highlight lessons learned from adapting this course for virtual learners during the coronavirus disease 2019 (COVID-19) pandemic.


Subject(s)
Computational Biology/education , Computational Biology/methods , Host-Parasite Interactions/physiology , Animals , COVID-19/pathology , Data Analysis , Genomics , High-Throughput Nucleotide Sequencing , Humans , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Plasmodium falciparum/physiology , Schistosoma mansoni/drug effects , Schistosoma mansoni/genetics , Schistosoma mansoni/physiology , Toxoplasma/drug effects , Toxoplasma/genetics , Toxoplasma/physiology
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