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Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques

The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. Howeve...

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Autores principales: Winkler, Michael, Gärtner, Sabine, Markus, Lara, Hoffmann, Markus, Nehlmeier, Inga, Krawczak, Michael, Sauermann, Ulrike, Pöhlmann, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827983/
https://www.ncbi.nlm.nih.gov/pubmed/31682595
http://dx.doi.org/10.1371/journal.pone.0224082
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author Winkler, Michael
Gärtner, Sabine
Markus, Lara
Hoffmann, Markus
Nehlmeier, Inga
Krawczak, Michael
Sauermann, Ulrike
Pöhlmann, Stefan
author_facet Winkler, Michael
Gärtner, Sabine
Markus, Lara
Hoffmann, Markus
Nehlmeier, Inga
Krawczak, Michael
Sauermann, Ulrike
Pöhlmann, Stefan
author_sort Winkler, Michael
collection PubMed
description The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.
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spelling pubmed-68279832019-11-12 Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques Winkler, Michael Gärtner, Sabine Markus, Lara Hoffmann, Markus Nehlmeier, Inga Krawczak, Michael Sauermann, Ulrike Pöhlmann, Stefan PLoS One Research Article The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques. Public Library of Science 2019-11-04 /pmc/articles/PMC6827983/ /pubmed/31682595 http://dx.doi.org/10.1371/journal.pone.0224082 Text en © 2019 Winkler et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Winkler, Michael
Gärtner, Sabine
Markus, Lara
Hoffmann, Markus
Nehlmeier, Inga
Krawczak, Michael
Sauermann, Ulrike
Pöhlmann, Stefan
Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques
title Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques
title_full Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques
title_fullStr Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques
title_full_unstemmed Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques
title_short Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques
title_sort role of rhesus macaque ifitm3(2) in simian immunodeficiency virus infection of macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827983/
https://www.ncbi.nlm.nih.gov/pubmed/31682595
http://dx.doi.org/10.1371/journal.pone.0224082
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