Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins.
Interferon-induced transmembrane proteins (IFITMs) can inhibit the cellular entry of several enveloped viruses, including simian immunodeficiency virus (SIV). The blockade of SIV by IFITMs is isolate specific, raising the question of which parameters impact sensitivity to IFITM. We show that the virion context in which SIV-Env is presented and the efficiency of virion incorporation determine Env susceptibility to inhibition by IFITMs. Thus, determinants other than the nature of the envelope protein can impact the IFITM sensitivity of viral entry.


OBJECTIVE
The host cell-encoded IFITM proteins can block viral entry and are an important component of the innate defenses against viral infection. However, the determinants controlling whether a virus is susceptible to blockade by IFITM proteins are incompletely understood. Our study shows that the amount of envelope proteins incorporated into virions as well as the nature of the virion particle itself can impact the sensitivity of viral entry to IFITMs. These results show for the first time that determinants other than the viral envelope protein can impact sensitivity to IFITM and have implications for the interpretation of previously published data on inhibition of viruses by IFITM proteins. Moreover, our findings might help to define the mechanism underlying the antiviral activity of IFITM proteins.
Infection Biology Unit, German Primate Center, Göttingen, Germany.
Florian
F
Wrensch
Infection Biology Unit, German Primate Center, Göttingen, Germany.
Markus
M
Hoffmann
Infection Biology Unit, German Primate Center, Göttingen, Germany.
Sabine
S
Gärtner
Infection Biology Unit, German Primate Center, Göttingen, Germany.
Inga
I
Nehlmeier
Infection Biology Unit, German Primate Center, Göttingen, Germany.
Michael
M
Winkler
Infection Biology Unit, German Primate Center, Göttingen, Germany spoehlmann@dpz.eu.
Stefan
http://orcid.org/0000-0001-6086-9136
S
Pöhlmann
D000818:Animals; D002460:Cell Line; D004198:Disease Susceptibility; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D016679:Genome, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion; D019065:Virus Assembly; D053586:Virus Internalization
D014759:Viral Envelope Proteins
IFITM; SIV; entry