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  1. Article ; Online: SERINC5: One antiviral factor to bind them all.

    Timilsina, Uddhav / Stavrou, Spyridon

    PLoS pathogens

    2023  Volume 19, Issue 1, Page(s) e1011076

    MeSH term(s) Humans ; Antiviral Agents/pharmacology ; Membrane Proteins/metabolism ; HIV-1/metabolism ; nef Gene Products, Human Immunodeficiency Virus/metabolism ; HIV Infections/metabolism
    Chemical Substances Antiviral Agents ; Membrane Proteins ; nef Gene Products, Human Immunodeficiency Virus ; SERINC5 protein, human
    Language English
    Publishing date 2023-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SERINC5

    Uddhav Timilsina / Spyridon Stavrou

    PLoS Pathogens, Vol 19, Iss 1, p e

    One antiviral factor to bind them all.

    2023  Volume 1011076

    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Determining the antiviral mechanism of MARCH2.

    Umthong, Supawadee / Timilsina, Uddhav / D'Angelo, Mary / Stavrou, Spyridon

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Membrane-associated RING-CH (MARCH) 2 protein is a member of the MARCH protein family of RING-CH finger E3 ubiquitin ligases that have important functions in regulating the levels of proteins found on the cell surface. MARCH1, 2 and 8 inhibit HIV-1 ... ...

    Abstract Membrane-associated RING-CH (MARCH) 2 protein is a member of the MARCH protein family of RING-CH finger E3 ubiquitin ligases that have important functions in regulating the levels of proteins found on the cell surface. MARCH1, 2 and 8 inhibit HIV-1 infection by preventing the incorporation of the envelope glycoproteins in nascent virions. However, a better understanding on the mechanism utilized by MARCH proteins to restrict HIV-1 is needed. In this report, we identify an amino acid in human MARCH2, that is absent in mouse MARCH2, critical for its antiretroviral function. Moreover, we map the domains of human MARCH2 critical for restricting as well as binding to the HIV-1 envelope glycoproteins. Our findings reveal important new aspects of the antiviral mechanism utilized by human MARCH2 to restrict HIV-1 that have potential implications to all MARCH proteins with antiviral functions.
    Language English
    Publishing date 2023-09-19
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.18.558306
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Construction and characterization of a full-length, replication-competent and infectious enhanced green fluorescence protein-tagged HIV-1 subtype C molecular clone.

    Rai, Madhu / Timilsina, Uddhav / Gaur, Ritu

    Virology

    2022  Volume 571, Page(s) 34–38

    Abstract: HIV-1 subtype C virus accounts for nearly 50% of the total HIV infections globally. Despite this high prevalence, our understanding of subtype C specific infections remains limited due to lack of an in vitro model system. This is the first report of ... ...

    Abstract HIV-1 subtype C virus accounts for nearly 50% of the total HIV infections globally. Despite this high prevalence, our understanding of subtype C specific infections remains limited due to lack of an in vitro model system. This is the first report of construction and characterization of a full-length and infectious EGFP-tagged HIV-1 subtype C molecular clone. The EGFP gene was inserted in-frame between the Nef and Env sequence in the HIV genome. The recombinant virus displayed expression of viral genes, infectivity and replication kinetics similar to the parental virus. VSV-G pseudotyping of the recombinant virus led to enhancement of HIV infection. The presence of the EGFP gene provides a rapid, easy and quantitative measure of HIV infection by flow cytometry and fluorescence microscopy. This clone will serve as an extremely beneficial tool to study HIV-1 subtype C specific infections.
    MeSH term(s) Clone Cells ; Fluorescence ; HIV Infections ; HIV-1/genetics ; Humans ; Virus Replication
    Language English
    Publishing date 2022-04-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2022.04.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.172: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Construction and characterization of a full-length, replication-competent and infectious enhanced green fluorescence protein-tagged HIV-1 subtype C molecular clone

    Rāya, Madhu / Timilsina, Uddhav / Gaur, Ritu

    Virology. 2022 June, v. 571 p.34-38

    2022  

    Abstract: HIV-1 subtype C virus accounts for nearly 50% of the total HIV infections globally. Despite this high prevalence, our understanding of subtype C specific infections remains limited due to lack of an in vitro model system. This is the first report of ... ...

    Abstract HIV-1 subtype C virus accounts for nearly 50% of the total HIV infections globally. Despite this high prevalence, our understanding of subtype C specific infections remains limited due to lack of an in vitro model system. This is the first report of construction and characterization of a full-length and infectious EGFP-tagged HIV-1 subtype C molecular clone. The EGFP gene was inserted in-frame between the Nef and Env sequence in the HIV genome. The recombinant virus displayed expression of viral genes, infectivity and replication kinetics similar to the parental virus. VSV-G pseudotyping of the recombinant virus led to enhancement of HIV infection. The presence of the EGFP gene provides a rapid, easy and quantitative measure of HIV infection by flow cytometry and fluorescence microscopy. This clone will serve as an extremely beneficial tool to study HIV-1 subtype C specific infections.
    Keywords HIV infections ; flow cytometry ; fluorescence microscopy ; genes ; green fluorescent protein ; pathogenicity ; virology ; viruses ; HIV-1 subtype C ; EGFP ; Infectious clone ; Reporter virus ; Full-length
    Language English
    Dates of publication 2022-06
    Size p. 34-38.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Use and reproduction
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2022.04.003
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 3686: Show issues

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  6. Article ; Online: SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5

    Uddhav Timilsina / Supawadee Umthong / Emily B. Ivey / Brandon Waxman / Spyridon Stavrou

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: ... phosphatydilserine biogenesis and a known retroviral restriction factor. Here, Timilsina et al. show that SERINC5 is ...

    Abstract SERINC5, is a cellular multipass transmembrane protein involved in sphingolipid and phosphatydilserine biogenesis and a known retroviral restriction factor. Here, Timilsina et al. show that SERINC5 is a host restriction factor for SARS-CoV-2 that prevents viral fusion during entry. Further they show that viral ORF7a counteracts SERINC5 anti-viral activity by blocking its incorporation into progeny virions.
    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions.

    Timilsina, Uddhav / Ivey, Emily B / Duffy, Sean / Plianchaisuk, Arnon / The Genotype To Phenotype Japan G P-Japan Consortium / Ito, Jumpei / Sato, Kei / Stavrou, Spyridon

    International journal of molecular sciences

    2024  Volume 25, Issue 4

    Abstract: A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine ( ... ...

    Abstract A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine (Y). Here, we evaluated the effect of this mutation on the three main functions ascribed to the SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize the type I interferon (IFN-I) response and to downregulate major histocompatibility complex I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein, resulting in changes in virus pathogenesis.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; COVID-19/genetics ; Interferon Type I/metabolism ; Mutation ; China
    Chemical Substances Interferon Type I
    Language English
    Publishing date 2024-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25042351
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  8. Article ; Online: SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5.

    Timilsina, Uddhav / Umthong, Supawadee / Ivey, Emily B / Waxman, Brandon / Stavrou, Spyridon

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2935

    Abstract: Serine Incorporator 5 (SERINC5), a cellular multipass transmembrane protein that is involved in sphingolipid and phosphatydilserine biogenesis, potently restricts a number of retroviruses, including Human Immunodeficiency Virus (HIV). SERINC5 is ... ...

    Abstract Serine Incorporator 5 (SERINC5), a cellular multipass transmembrane protein that is involved in sphingolipid and phosphatydilserine biogenesis, potently restricts a number of retroviruses, including Human Immunodeficiency Virus (HIV). SERINC5 is incorporated in the budding virions leading to the inhibition of virus infectivity. In turn, retroviruses, including HIV, encode factors that counteract the antiviral effect of SERINC5. While SERINC5 has been well studied in retroviruses, little is known about its role in other viral families. Due to the paucity of information regarding host factors targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), we evaluated the effect of SERINC proteins on SARS-CoV-2 infection. Here, we show SERINC5 inhibits SARS-CoV-2 entry by blocking virus-cell fusion, and SARS-CoV-2 ORF7a counteracts the antiviral effect of SERINC5 by blocking the incorporation of over expressed SERINC5 in budding virions.
    MeSH term(s) Antiviral Agents/pharmacology ; COVID-19 ; HIV Infections ; Humans ; Membrane Proteins ; SARS-CoV-2 ; Virion/physiology
    Chemical Substances Antiviral Agents ; Membrane Proteins ; SERINC5 protein, human
    Language English
    Publishing date 2022-05-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30609-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: SERINC5 Potently Restricts Retrovirus Infection

    Timilsina, Uddhav / Umthong, Supawadee / Lynch, Brian / Stablewski, Aimee / Stavrou, Spyridon

    mBio

    2020  Volume 11, Issue 4

    Abstract: ... ...

    Abstract The
    MeSH term(s) Animals ; Female ; Glycosylation ; Host-Pathogen Interactions ; Leukemia Virus, Murine/pathogenicity ; Leukemia, Experimental/virology ; Male ; Membrane Glycoproteins/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Retroviridae Infections/virology ; Tumor Virus Infections/virology
    Chemical Substances Membrane Glycoproteins ; Membrane Proteins ; Serinc3 protein, mouse ; Serinc5 protein, mouse
    Language English
    Publishing date 2020-07-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.00588-20
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  10. Article ; Online: SARS-CoV-2 ORF7a mutation found in BF.5 and BF.7 sublineages impacts its functions

    Timilsina, Uddhav / Duffy, Sean / Plianchaisuk, Arnon / Ito, Jumpei / Sato, Kei / Stavrou, Spyridon

    bioRxiv

    Abstract: A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of ORF7a: H47Y mutation. Here we evaluated the effect of this mutation on the three main functions ascribed to SARS- ... ...

    Abstract A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of ORF7a: H47Y mutation. Here we evaluated the effect of this mutation on the three main functions ascribed to SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize type-I interferon (IFN-I) response and to downregulate Major Histocompatibility Complex-I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein resulting in changes in virus pathogenesis.
    Keywords covid19
    Language English
    Publishing date 2023-09-07
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.09.06.556547
    Database COVID19

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