Expression levels of Fv1: effects on retroviral restriction specificities
File(s)
Author(s)
Li, W
Yap, MW
Voss, V
Stoye, JP
Type
Journal Article
Abstract
Background The mouse protein Fv1 is a factor that can confer resistance to retroviral infection. The two major Fv1 alleles from laboratory mice, Fv1 n and Fv1 b , restrict infection by different murine leukaemia viruses (MLVs). Fv1n restricts B-tropic MLV, but not N-tropic MLV or NB-tropic MLV. In cells expressing Fv1b at natural levels, only N-MLV is restricted, however restriction of NB-MLV and partial restriction of B-MLV were observed when recombinant Fv1b was expressed from an MLV promoter in Fv1 null Mus dunni tail fibroblast cells. To investigate the relationship between expression level and restriction specificity we have developed new retroviral delivery vectors which allow inducible expression of Fv1, and yet allow sufficient production of fluorescent reporter proteins for analysis in our FACS-based restriction assay. Results We demonstrated that at concentrations close to the endogenous expression level, Fv1b specifically restricts only N-MLV, but restriction of NB-MLV, and to a lesser extent B-MLV, could be gained by increasing the protein level of Fv1b. By contrast, we found that even when Fv1n is expressed at very high levels, no significant inhibition of N-MLV or NB-MLV could be observed. Study of Fv1 mutants using this assay led to the identification of determinants for N/B tropism at an expression level close to that of endogenous Fv1n and Fv1b. We also compared the recently described restriction activities of wild mice Fv1 proteins directed against non-MLV retroviruses when expressed at different levels. Fv1 from M. spretus restricted N-MLV, B-MLV and equine infectious anaemia virus equally even at low concentrations, while Fv1 from M. macedonicus showed even stronger restriction against equine infectious anaemia virus than to N-MLV. Restriction of feline foamy virus by Fv1 of M. caroli occurred at levels equivalent to MLV restriction. Conclusions Our data indicate that for some but not all Fv1 proteins, gain of restriction activities could be achieved by increasing the expression level of Fv1. However such a concentration dependent effect is not seen with most Fv1s and cannot explain the recently reported activities against non-MLVs. It will be interesting to examine whether overexpression of other capsid binding restriction factors such as TRIM5α or Mx2 result in novel restriction specificities.
Date Issued
2016-06-24
Online Publication Date
2016-06-24
2018-04-25T15:21:34Z
Date Acceptance
2016-06-16
ISSN
1742-4690
Publisher
BIOMED CENTRAL LTD
Journal / Book Title
RETROVIROLOGY
Volume
13
Issue
1
Copyright Statement
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(
http://creativecommons.org/licenses/by/4.0/
), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (
http://creativecommons.org/
publicdomain/zero/1.0/
) applies to the data made available in this article, unless otherwise stated.
(
http://creativecommons.org/licenses/by/4.0/
), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (
http://creativecommons.org/
publicdomain/zero/1.0/
) applies to the data made available in this article, unless otherwise stated.
Source Database
web-of-science
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000378598400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Virology
Fv1
Restriction specificity
Inducible expression
Murine leukaemia virus
MURINE LEUKEMIA-VIRUS
ANTIRETROVIRAL ACTIVITY
TRIM5-ALPHA DETERMINES
RESPONSIVE PROMOTERS
GENETIC TRANSMISSION
PRIMATE TRIM5-ALPHA
B30.2(SPRY) DOMAIN
POSITIVE SELECTION
CAPSID PROTEIN
B30.2 DOMAIN
Animals
Capsid Proteins
Cell Line
Genetic Vectors
Humans
Leukemia Virus, Murine
Mice
Mutation
Proteins
Virus Replication
1103 Clinical Sciences
Publication Status
Published
Article Number
ARTN 42