Protein Arginine <i>N</i>-methyltransferases 5 and 7 Promote HIV-1 Production

• Main Authors: Hironobu Murakami, Takehiro Suzuki, Kiyoto Tsuchiya, Hiroyuki Gatanaga, Manabu Taura, Eriko Kudo, Seiji Okada, Masami Takei, Kazumichi Kuroda, Tatsuo Yamamoto, Kyoji Hagiwara, Naoshi Dohmae, Yoko Aida
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Viruses
• Subjects: hiv-1; vpr; prmt5; prmt7; vpr-binding protein; virus production; stability; macrophage; pathogenesis
• Online Access: https://www.mdpi.com/1999-4915/12/3/355

Current therapies for human immunodeficiency virus type 1 (HIV-1) do not completely eliminate viral reservoirs in cells, such as macrophages. The HIV-1 accessory protein viral protein R (Vpr) promotes virus production in macrophages, and the maintenance of Vpr is essential for HIV-1 replication in these reservoir cells. We identified two novel Vpr-binding proteins, i.e., protein arginine <i>N</i>-methyltransferases (PRMTs) 5 and 7, using human monocyte-derived macrophages (MDMs). Both proteins found to be important for prevention of Vpr degradation by the proteasome; in the context of PRMT5 and PRMT7 knockdowns, degradation of Vpr could be prevented using a proteasome inhibitor. In MDMs infected with a wild-type strain, knockdown of PRMT5/PRMT7 and low expression of PRMT5 resulted in inefficient virus production like Vpr-deficient strain infections. Thus, our findings suggest that PRMT5 and PRMT7 support HIV-1 replication via maintenance of Vpr protein stability.