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


Autoři: Michael Winkler aff001;  Sabine Gärtner aff001;  Lara Markus aff001;  Markus Hoffmann aff001;  Inga Nehlmeier aff001;  Michael Krawczak aff003;  Ulrike Sauermann aff004;  Stefan Pöhlmann aff001
Působiště autorů: Infection Biology Unit, German Primate Center–Leibniz Institute for Primate Research, Göttingen, Germany aff001;  Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany aff002;  Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany aff003;  Infection Models Unit, German Primate Center—Leibniz Institute for Primate Research, Göttingen, Germany aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224082

Souhrn

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.

Klíčová slova:

293T cells – Cell cultures – HIV infections – Host cells – Macaque – Polymerase chain reaction – Rhesus monkeys – SIV


Zdroje

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2019 Číslo 11