Comparison of the Effects of Retroviral Restriction Factors Involved in Resistance to Porcine Endogenous Retrovirus
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Three major classes of retroviral restriction factors (APOBEC3G, Tetherin, and TRIM5α) havebeen identified in mammals. Restriction factors are cellular proteins that are able to limit viralreplication by targeting specific steps of the viral life cycle. To evaluate which restriction factoris the most effective to inhibit the replication of porcine endogenous retroviruses (PERVs), theantiviral activity of each restriction factor was compared. In pseudotype assay, the antiviralactivity of human tetherin against PERV pseudotype was slightly weaker than that of humanAPOBEC3G (hA3G). A combination of tetherin and hA3G was more potent than eachindividual restriction factor. We questioned whether a combination of tetherin and hA3Gcould also inhibit the spreading replication of PERV. In agreement with the pseudotype assay,two restriction factors inhibit infectious PERV replication in a spreading infection. In thisstudy, hA3G could strongly inhibit the replication of PERV, but tetherin modestly restricted it. Based on these results, we concluded that a combination of tetherin and hA3G is the mosteffective way to restrict PERV. A combination of different restriction factors will encouragethe development of a new approach to treat retroviral disease.
Abstract
Three major classes of retroviral restriction factors (APOBEC3G, Tetherin, and TRIM5α) havebeen identified in mammals. Restriction factors are cellular proteins that are able to limit viralreplication by targeting specific steps of the viral life cycle. To evaluate which restriction factoris the most effective to inhibit the replication of porcine endogenous retroviruses (PERVs), theantiviral activity of each restriction factor was compared. In pseudotype assay, the antiviralactivity of human tetherin against PERV pseudotype was slightly weaker than that of humanAPOBEC3G (hA3G). A combination of tetherin and hA3G was more potent than eachindividual restriction factor. We questioned whether a combination of tetherin and hA3Gcould also inhibit the spreading replication of PERV. In agreement with the pseudotype assay,two restriction factors inhibit infectious PERV replication in a spreading infection. In thisstudy, hA3G could strongly inhibit the replication of PERV, but tetherin modestly restricted it. Based on these results, we concluded that a combination of tetherin and hA3G is the mosteffective way to restrict PERV. A combination of different restriction factors will encouragethe development of a new approach to treat retroviral disease.
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