Abstract
The virus–host protein interactions that underlie respiratory syncytial virus (RSV) assembly are still not completely defined, despite almost 60 years of research. RSV buds from the apical surface of infected cells, once virion components have been transported to the budding sites. Association of RSV matrix (M) protein with the actin cytoskeleton may play a role in facilitating this transport. We have investigated the interaction of M with actin in vitro and cell culture. Purified wildtype RSV M protein was found to bind directly to polymerized actin in vitro. Vero cells were transfected to express full-length M (1–256) as a green fluorescent protein-(GFP) tagged protein, followed by treatment with the microfilament destabilizer, cytochalasin D. Destabilization of the microfilament network resulted in mislocalization of full-length M, from mostly cytoplasmic to diffused across both cytoplasm and nucleus, suggesting that M interacts with microfilaments in this system. Importantly, treatment of RSV-infected cells with cytochalasin D results in lower infectious virus titers, as well as mislocalization of M to the nucleus. Finally, using deletion mutants of M in a transfected cell system, we show that both the N- and C-terminus of the protein are required for the interaction. Together, our data suggest a possible role for M–actin interaction in transporting virion components in the infected cell.
Highlights
Respiratory syncytial virus (RSV) is a major pathogen responsible for lower respiratory tract infections (LRTI) in infants, young children, the immunosuppressed, and the elderly [1,2]
respiratory syncytial virus (RSV)-infected cells were treated with cytochalasin D at early (6–18 h) or late (18–30 h) times in infection, and samples were collected at 48 h post-infection
We have shown that the RSV M protein interacts with actin in vitro and in cell culture, and that microfilaments have a role in the subcellular localization of M protein
Summary
Respiratory syncytial virus (RSV) is a major pathogen responsible for lower respiratory tract infections (LRTI) in infants, young children, the immunosuppressed, and the elderly [1,2]. Patients with RSV infections present with clinical complications, such as pneumonia and bronchiolitis [3]. A significant challenge to RSV treatment and prevention is absence of available antiviral drugs and vaccines that effectively target infections [1,4]. RSV is an enveloped virus with a negative-sense single-stranded RNA genome, belonging to the Pneumovirus genus of the Pneumoviridae family [5,6]. The RSV genome encodes 11 proteins and is tightly encapsidated with the nucleocapsid, which is composed of the nucleocapsid (N) protein, RNA polymerase (L) and its cofactor phosphoprotein (P), as well as the M2-1 protein [5,7]. The genome encodes the envelope glycoproteins fusion protein (F), glycoprotein (G) and small hydrophobic protein (SH), two non-structural proteins (NS1 and NS2), the M2-2 protein, and the matrix protein (M)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
