Annexin A2 is involved in the production of classical swine fever virus infectious particles

Abstract

Annexin A2 (ANXA2) is an important host factor regulating several key processes in many viruses. To evaluate the potential involvement of ANXA2 in the life cycle of classical swine fever virus (CSFV), an RNA interference (RNAi) approach was utilized. Knockdown of ANXA2 did not impair CSFV RNA replication but significantly reduced CSFV production. A comparable reduction of extracellular and intracellular infectivity levels was detected, indicating that ANXA2 might play a role in CSFV assembly rather than in genome replication and virion release. Furthermore, ANXA2 was found to bind CSFV NS5A, an essential replicase component. Amino acids R338, N359, G378 of NS5A were revealed to be pivotal for the ANXA2-NS5A interaction. Substitutions of these amino acids had no effect on viral RNA replication but substantially reduced CSFV production, which might partly be due to these mutations destroying the ANXA2-NS5A interaction. These results suggested that ANXA2 might participate in CSFV production process by binding NS5A.

The Molecular Biology of Pestiviruses

“…Among them, yeast two-hybrid (Y2H) searches with individual viral proteins are the most frequently used (Doceul et al, 2008;Gladue, Baker-Bransetter, et al, 2014;Johns et al, 2010;Kang et al, 2012;Zahoor et al, 2010) followed by microarray techniques Yamane et al, 2009c). Other approaches relied on targeting possible interaction partners of viral proteins or RNA Fu, Shi, Shi, Meng, Bao, et al, 2014;He et al, 2012;Jordan, Nikolaeva, et al, 2002;Lin et al, 2014;Mohamed et al, 2014;Sheng et al, 2015;Wang et al, 2011;Yamane et al, 2009aYamane et al, , 2009b. Some of this work needs further evaluation and elaboration to allow establishment of a hypothesis on the specific function of the host factors.…”

“…For CSFV, enhancement of replication was described to follow induction of autophagic processes (Pei et al, 2014). Further cellular factors interacting with pestiviral proteins are Annexin A2 (interacts with NS5A and is involved in particle production) (Sheng et al, 2015), sphingosine kinase (interacts with NS3 and is thereby inhibited resulting in enhanced virus replication) (Yamane et al, 2009b), adenosine deaminase acting on RNA (ADAR) (interacts with NS4A, overexpression reduces BVDV replication) (Mohamed et al, 2014), and the porcine homologue of human antigen R (HuR) (binds to AU-rich sequences in the 3 0 -NTR of CSFV RNA and might stabilize the RNA) (Nadar et al, 2011). Another group of factors interacts with the core protein, namely the ER-associated degradation pathway protein OS9 and the IQGAP1 protein.…”

Complex Virus–Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview

“…Anx2 interacts with E2 and promotes CSFV production [ 69 ], and treatment of PK-15 cells with Anx2-specific polyclonal antibody significantly inhibited CSFV growth, thus we presume that Anx2 likely participates in the virus attachment or entry. In addition, interaction between Anx2 and NS5A enhances the virus assembly rather than in genome replication and virion release [ 70 ]. It is possible that Anx2 participates in the multiple steps of the CSFV life cycles.…”

“…Cytoplasmic RNA helicase A (RHA) participates in the modulation of RNA synthesis, replication, and translation of CSFV through binding 5′- and 3′-NCRs [ 75 ]. Anx2 has been shown to interact with E2 and NS5A, enhancing viral growth and assembly [ 69 , 70 ]. Thus, we speculate that Anx2 plays critical roles in the multiple phases of the virus life cycle.…”

Annexin A2 Mediates the Localization of Measles Virus Matrix Protein at the Plasma Membrane

“…Given the diverse functions of AnxA2, it is not surprising that AnxA2 is involved in different replication processes of many viruses, including hepatitis C virus (HCV) (14,15), human immunodeficiency virus (HIV) (16,17), human papillomavirus (HPV) (18,19), enterovirus 71 (20), bluetongue virus (21), and classical swine fever virus (22). In this study, we examined whether AnxA2 plays any role in MV replication.…”