Identification of Interferon-Stimulated Genes with Antiretroviral Activity

Melissa Kane; Trinity M. Zang; Suzannah J. Rihn; Fengwen Zhang; Tonya Kueck; Mudathir Alim; John Schoggins; Charles M. Rice; Sam J. Wilson; Paul D. Bieniasz

doi:10.1016/j.chom.2016.08.005

Identification of Interferon-Stimulated Genes with Antiretroviral Activity

Melissa Kane, Trinity M. Zang, Suzannah J. Rihn, Fengwen Zhang, Tonya Kueck, Mudathir Alim, John Schoggins, Charles M. Rice, Sam J. Wilson, Paul D. Bieniasz

Research output: Contribution to journal › Article › peer-review

159 Scopus citations

Abstract

Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.

Original language	English (US)
Pages (from-to)	392-405
Number of pages	14
Journal	Cell Host and Microbe
Volume	20
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2016.08.005
State	Published - Sep 14 2016

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

Access to Document

10.1016/j.chom.2016.08.005

Cite this

@article{aaad177ee36c4f06a0469421807f5cb0,

title = "Identification of Interferon-Stimulated Genes with Antiretroviral Activity",

abstract = "Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.",

author = "Melissa Kane and Zang, {Trinity M.} and Rihn, {Suzannah J.} and Fengwen Zhang and Tonya Kueck and Mudathir Alim and John Schoggins and Rice, {Charles M.} and Wilson, {Sam J.} and Bieniasz, {Paul D.}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = sep,

day = "14",

doi = "10.1016/j.chom.2016.08.005",

language = "English (US)",

volume = "20",

pages = "392--405",

journal = "Cell Host and Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Identification of Interferon-Stimulated Genes with Antiretroviral Activity

AU - Kane, Melissa

AU - Zang, Trinity M.

AU - Rihn, Suzannah J.

AU - Zhang, Fengwen

AU - Kueck, Tonya

AU - Alim, Mudathir

AU - Schoggins, John

AU - Rice, Charles M.

AU - Wilson, Sam J.

AU - Bieniasz, Paul D.

PY - 2016/9/14

Y1 - 2016/9/14

N2 - Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.

AB - Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.

UR - http://www.scopus.com/inward/record.url?scp=84995603714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995603714&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2016.08.005

DO - 10.1016/j.chom.2016.08.005

M3 - Article

C2 - 27631702

AN - SCOPUS:84995603714

SN - 1931-3128

VL - 20

SP - 392

EP - 405

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

Identification of Interferon-Stimulated Genes with Antiretroviral Activity

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this