Equine Schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism

Abstract

Human schlafen11 is a novel restriction factor for HIV-1 based on bias regarding relative synonymous codon usage (RSCU). Here, we report the cloning of equine schlafen11 (eSLFN11) and the characteristics of its role in restricting the production of equine infectious anemia virus (EIAV), a retrovirus similar to HIV-1. Overexpression of eSLFN11 inhibited EIAV replication, whereas knockdown of endogenous eSLFN11 by siRNA enhanced the release of EIAV from its principal target cell. Notably, although eSLFN11 significantly suppressed expression of viral Gag protein and EIAV release into the culture medium, the levels of intracellular viral early gene proteins Tat and Rev and viral genomic RNA were unaffected. Coincidently, similar altered patterns of codon usage bias were observed for both the early and late genes of EIAV. Therefore, our data suggest that eSLFN11 restricts EIAV production by impairing viral mRNA translation via a mechanism that is similar to that employed by hSLFN11 for HIV-1.