Discovery and characterization of novel Nef-like infectivity factor

The SERINC family is a highly conserved group of genes which in the human genome comprises 5 members, encoding five homologous multipass transmembrane proteins. SERINC5, and to a lesser extent SERINC3, are powerful inhibitors of Human immunodeficiency virus 1 (HIV-1). SERINC5, expressed in virus-producing cells, is incorporated into the envelope of newly formed retroviral particles and inhibits an early stage of the virus infection process of the target cell, by preventing the delivery of the retroviral core into the target cell cytoplasm. Nef, an accessory protein of HIV-1, counteracts the antiretroviral activity of SERINC5 by promoting its endocytosis, which results in its removal from the cell surface, preventing its incorporation into retroviral particles. SERINC5 inhibits not only HIV-1, but also other divergent retroviruses, such as Murine leukemia virus (MLV). During my Ph.D. studies I demonstrated that the S2 auxiliary protein from Equine infectious anemia virus (EIAV) functionally resembles Nef and MLV glycoGag and counteracts SERINC5 with a similar mechanism. While the inhibitory effect of SERINC5 has been established on retroviruses, nothing is yet known about its effect on other viruses. Here I describe evidence which indicates the possible inhibitory activity of the SERINC gene family against other RNA viruses.