Endoplasmic Reticulum-Shaping Atlastin Proteins Facilitate KSHV Replication

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) has two life cycle modes: the latent and lytic phases. The endoplasmic reticulum (ER) is the site for KSHV production. Furthermore, ER stress can trigger reactivation of KSHV. Little is known about the nature of the ER factors that regulate KSHV replication. Atlastin proteins (ATLs which include ATL1, ATL2, and ATL3) are large dynamin-related GTPases that control the structure and the dynamics of the ER membrane. Here, we show that ATLs can regulate KSHV lytic activation and infection. Overexpression of ATLs enhances KSHV lytic activation, whereas ATLs silence inhibits it. Intriguingly, we find that silencing of ATLs impairs the response of cells to ER stress, and ER stress can promote the lytic activation of KSHV. Our study establishes that ATLs plays a critically regulatory role in KSHV infection, thus expanding the known scope of biological processes controlled by ATLs to include KSHV infection.

Host Subcellular Organelles: Targets of Viral Manipulation

“…Recent studies have reported the interactions between viral infection and host cellular ER-shaping proteins such as ATL3, RTN3, and Lunapark, which are involved in ER network formation [167]. ER-shaping atlastin proteins (ATL1, -2, and -3), which induce ER membrane fusion, are recruited to the Zika virus (ZIKV) replication site and co-localized with the viral proteins, facilitating ZIKV replication [168]. ATL3s can also regulate Kaposi's sarcoma-associated herpesvirus (KSHV) lytic activation and infection [169].…”