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

Abstract

Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca-dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca-binding protein S100A10. Measles virus (MV), a member of the family , is an enveloped virus with a nonsegmented negative strand RNA genome. Knockdown of AnxA2 greatly reduced MV growth in cells, without affecting its entry and viral RNA production. In MV-infected, AnxA2-knockdown cells, the expression level of the matrix (M) protein, but not other viral proteins, was reduced compared with that in control cells, and the distribution of the M protein at the plasma membrane was decreased. The M protein lines the inner surface of the envelope and plays an important role in virus assembly by connecting the nucleocapsid to the envelope proteins. The M protein bound to AnxA2 independently of AnxA2's phosphorylation or its association with S100A10, and was co-localized with AnxA2 within cells. Truncation of the N-terminal 10 amino acid residues, but not the N-terminal 5 residues, compromised the ability of the M protein to interact with AnxA2 and localize at the plasma membrane. These results indicate that AnxA2 mediates the localization of the MV M protein at the plasma membrane by interacting with its N-terminal region (especially residues at positions 6-10), thereby aiding in MV assembly. Measles virus (MV) is an important human pathogen, still claiming ∼ 100,000 lives per year despite the presence of effective vaccines, and causes occasional outbreaks even in developed countries. Replication of viruses largely relies on the functions of host cells. Our study revealed that the reduction of the host protein annexin A2 compromises the replication of MV within the cell. Further studies demonstrated that annexin A2 interacts with the MV matrix (M) protein and mediates the localization of the M protein at the plasma membrane where MV particles are formed. The M protein lines the inner surface of the MV envelope membrane and plays a role in MV particle formation. Our results provide useful information for the understanding of the MV replication process and potential development of anti-viral agents.

Chaperones, Membrane Trafficking and Signal Transduction Proteins Regulate Zaire Ebola Virus trVLPs and Interact With trVLP Elements

“…However, interactions of 14-3-3 proteins with EBOV have not been reported previously. Similarly, annexin family proteins also interact closely with RNA viruses such as measles virus and H5N1 avian influenza virus ( Ma et al, 2017 ; Koga et al, 2018 ), but interactions with EBOV have not been reported previously. MAP kinases are essential in signal transduction and involved in numerous virus life cycle events, including in EBOV ( Strong et al, 2008 ; Johnson et al, 2014 ), but the detailed mechanisms of interactions between MAP kinases and EBOV remain ambiguous.…”

Chicken bromodomain-containing protein 2 interacts with the Newcastle disease virus matrix protein and promotes viral replication

“…In addition, the angiomotin-like 1 protein interacts with the parainfluenza virus 5 (PIV5) M protein [ 34 ] and acts as a linker between the PIV5 M and NEDD4 ubiquitin ligases [ 35 ], which reveals a novel host factor recruitment strategy for paramyxoviruses to achieve VLP production and virus budding. Moreover, a recent study showed that annexin A2 interacting with the measles virus (MeV) M protein mediates the plasma membrane localization of the M protein and assists the assembly and budding of progeny virions [ 36 ]. All of these findings accelerate our understanding of the potential functions of paramyxovirus M proteins.…”

GroEL Protein (Heat Shock Protein 60) of Mycoplasma gallisepticum Induces Apoptosis in Host Cells by Interacting with Annexin A2

“…Annexin A2, which belongs to the annexin superfamily, is predominantly expressed at the plasma membrane but is also present on intracellular vesicles and in the nucleus (27). Annexin A2 is involved in multiple cellular processes, including DNA replication, cell proliferation, cell adhesion, and apoptosis (28)(29)(30)(31).…”