Sumoylation of Human Parainfluenza Virus Type 3 Phosphoprotein Correlates with A Reduction in Viral Replication
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RESEARCH ARTICLE
Sumoylation of Human Parainfluenza Virus Type 3 Phosphoprotein Correlates with A Reduction in Viral Replication Qi Cheng1 • Wenjing Huai1 • Xiaoyan Wu1 • Mingzhou Chen1 Received: 11 September 2020 / Accepted: 29 September 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract Human parainfluenza virus type 3 (HPIV3), a member of the Paramyxoviridae family, can cause lower respiratory disease in infants and young children. The phosphoprotein (P) of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein (L). P connects nucleocapsid protein (N) with L to initiate genome transcription and replication. Sumoylation influences many important pathways of the target proteins, and many viral proteins are also themselves sumoylated. In this study, we found that the P of HPIV3 could be sumoylated, and mutation of K492 and K532 to arginine (PK492R/K532R) failed to be sumoylated within P, which enhances HPIV3 minigenome activity. Biochemical studies showed that PK492R/K532R had no effect on its interactions with N, formation of homo-tetramers and formation of inclusion bodies. Finally, we found that incorporation of K492R/K532R into a recombinant HPIV3 (rHPIV3-PK492R/K532R) increased viral production in culture cells, suggesting that sumoylation attenuates functions of P and down-regulates viral replication. Keywords Human parainfluenza virus type 3 (HPIV3) Phosphoprotein Sumoylation Replication Viral replication
Introduction Human parainfluenza virus type 3 (HPIV3) belongs to the Paramyxoviridae family and can cause lower respiratory disease in infants and young children (Moscona 2005). However, no effective vaccine and antivirals have been developed or licensed. The genome of HPIV3 encodes nucleoprotein (N), phosphoprotein (P), RNA-dependent RNA polymerase large protein (L), matrix protein (M), and two spike glycoproteins hemagglutinin-neuraminidase protein (HN) and fusion protein (F) (Banerjee et al. 1991). N encapsidates viral genome RNA to form N-RNA templates, and P, as a cofactor of L, recruits the L to N-RNA template for initiation of genome transcription and replication (Durbin et al. 1997; Galinski 1991). In addition, P functions as a chaperone to interact with N to prevent the nonspecific aggregation of N and N binding to cellular RNAs (Chen et al. 2007; Howard and Wertz 1989). & Mingzhou Chen [email protected] 1
State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China
Moreover, interaction of N and P provides the minimal requirement for the formation of inclusion bodies which are critical for viral replication (Zhang et al. 2013), and functionally deficient P severely affects the formation of inclusion bodies (Zhang et al. 2018). Sumoylation is similar to the ubiquitination process (Matunis et al. 1996), but the functional effect of sumoylation and ubiquitination could be completely diverse (Gill 2004)
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