PT - JOURNAL ARTICLE AU - Weidong Xiong AU - Deisy Contreras AU - Joseph Ignatius Irudayam AU - Ayub Ali AU - Otto O. Yang AU - Vaithilingaraja Arumugaswami TI - C19ORF66 is an Interferon-Stimulated Gene (ISG) which Inhibits Human Immunodeficiency Virus-1 AID - 10.1101/050310 DP - 2016 Jan 01 TA - bioRxiv PG - 050310 4099 - http://biorxiv.org/content/early/2016/04/26/050310.short 4100 - http://biorxiv.org/content/early/2016/04/26/050310.full AB - Innate immunity is the first line of defense against invading microbes1. The type I interferon (IFN) pathway plays a key role in controlling Human Immunodeficiency Virus type 1 (HIV-1) replication2,3. We identified an IFN-α stimulated gene C19ORF66 that we term Suppressor of Viral Activity (SVA). Full length SVA-1 protein inhibits HIV-1 by blocking virion production. SVA splice variants truncated at the C-terminus and/or disrupted at the nuclear export signal (NES) lose antiviral activity and localize to nucleus, while full length SVA-1 co-localizes with HIV-1 p24 protein in the cytoplasmic compartment of infected cells. SVA-1 is structurally and functionally conserved across species, including mouse and chimpanzee. We provide the first description of the effector function of the gene SVA/C190RF66 as an innate immune factor with anti-HIV-1 activity.