Replacement of feline foamy virus bet by feline immunodeficiency virus vif yields replicative virus with novel vaccine candidate potential

Retrovirology
Carmen Ledesma-FelicianoMartin Löchelt

Abstract

Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes. Here we examine the capacity of vif to substitute for bet function in a chimeric FFV to assess the transferability of anti-feA3 factors to allow viral replication. We show that vif can replace bet to yield replication-competent chimeric foamy viruses. An in vitro selection screen revealed that an engineered Bet-Vif fusion protein yields suboptimal protection against feA3. After multiple passages through feA3-expressing cells, however, variants with optimized replication competence emerged. In these variants, Vif was expressed independently from an N-terminal Bet moiety and was stably maintai...Continue Reading

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Citations

Feb 6, 2019·Viruses·Ottmar HerchenröderDirk Lindemann
Mar 25, 2020·Viruses·Emmanouil SimantirakisGeorge Vassilopoulos
Nov 27, 2019·Viruses·Magdalena Materniak-KornasMartin Löchelt
Feb 2, 2020·Scientific Reports·Nicholas G DannemillerScott Carver
Apr 4, 2021·Viruses·Ananda Ayyappan Jaguva VasudevanCarsten Münk
Jun 3, 2021·Viruses·Hirohisa MekataTakayuki Miyazawa

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Methods Mentioned

BETA
deamination
transfection
PCR
nucleotide exchange
ELISA
ELISAs
PCRs
since
light microscopy

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