دورية أكاديمية
أعرض في EDS

Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus.

التفاصيل البيبلوغرافية
العنوان: Genome-Wide Knockout Screen Identifies Human Sialomucin CD164 as an Essential Entry Factor for Lymphocytic Choriomeningitis Virus.
المؤلفون: Liu J; Department of Biochemistry and Biophysics, University of California, San Franciscogrid.266102.1, San Francisco, California, USA.; University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, California, USA., Knopp KA; Department of Biochemistry and Biophysics, University of California, San Franciscogrid.266102.1, San Francisco, California, USA., Rackaityte E; Department of Biochemistry and Biophysics, University of California, San Franciscogrid.266102.1, San Francisco, California, USA., Wang CY; Chan Zuckerberg Biohub, San Francisco, California, USA., Laurie MT; Department of Biochemistry and Biophysics, University of California, San Franciscogrid.266102.1, San Francisco, California, USA., Sunshine S; Department of Biochemistry and Biophysics, University of California, San Franciscogrid.266102.1, San Francisco, California, USA., Puschnik AS; Chan Zuckerberg Biohub, San Francisco, California, USA., DeRisi JL; Department of Biochemistry and Biophysics, University of California, San Franciscogrid.266102.1, San Francisco, California, USA.; Chan Zuckerberg Biohub, San Francisco, California, USA.
المصدر: MBio [mBio] 2022 Jun 28; Vol. 13 (3), pp. e0020522. Date of Electronic Publication: 2022 May 03.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Endolyn*/genetics , Lymphocytic Choriomeningitis*/pathology , Lymphocytic choriomeningitis virus*/pathogenicity, Cysteine ; Female ; Humans ; Placenta/virology ; Pregnancy ; Sialomucins
مستخلص: Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. However, our understanding of LCMV and its interactions with human host factors remains incomplete. Here, host determinants affecting LCMV infection were investigated through a genome-wide CRISPR knockout screen in A549 cells, a human lung adenocarcinoma line. We identified and validated a variety of novel host factors that play a functional role in LCMV infection. Among these, knockout of the sialomucin CD164, a heavily glycosylated transmembrane protein, was found to ablate infection with multiple LCMV strains but not other hemorrhagic mammarenaviruses in several cell types. Further characterization revealed a dependency of LCMV entry on the cysteine-rich domain of CD164, including an N-linked glycosylation site at residue 104 in that region. Given the documented role of LCMV with respect to transplacental human infections, CD164 expression was investigated in human placental tissue and placental cell lines. CD164 was found to be highly expressed in the cytotrophoblast cells, an initial contact site for pathogens within the placenta, and LCMV infection in placental cells was effectively blocked using a monoclonal antibody specific to the cysteine-rich domain of CD164. Together, this study identifies novel factors associated with LCMV infection of human tissues and highlights the importance of CD164, a sialomucin that previously had not been associated with viral infection. IMPORTANCE Lymphocytic choriomeningitis virus (LCMV) is a human-pathogenic mammarenavirus that can be fatal in congenital infections. Although frequently used in the study of persistent infections in the field of immunology, aspects of this virus's life cycle remain incomplete. For example, while viral entry has been shown to depend on a cell adhesion molecule, DAG1, genetic knockout of this gene allows for residual viral infection, implying that additional receptors can mediate cell entry. The significance of our study is the identification of host factors important for successful infection, including the sialomucin CD164, which had not been previously associated with viral infection. We demonstrated that CD164 is essential for LCMV entry into human cells and can serve as a possible therapeutic target for treatment of congenital infection.
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معلومات مُعتمدة: F31 AI150007 United States AI NIAID NIH HHS; T32 AI060537 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: CD164; CRISPR screen; lymphocytic choriomeningitis virus; viral entry
المشرفين على المادة: 0 (CD164 protein, human)
0 (Endolyn)
0 (Sialomucins)
K848JZ4886 (Cysteine)
تواريخ الأحداث: Date Created: 20220503 Date Completed: 20220630 Latest Revision: 20230313
رمز التحديث: 20230313
مُعرف محوري في PubMed: PMC9239079
DOI: 10.1128/mbio.00205-22
PMID: 35502904
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.00205-22