Structure and Function of the Human Respiratory Syncytial Virus M2–1 Protein

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

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Fatty Acid Acylation of the Fusion Glycoprotein of Human Respiratory Syncytial Virus

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)81623-4 ◽

1989 ◽

Vol 264 (18) ◽

pp. 10339-10342

Author(s):

R G Arumugham ◽

R C Seid ◽

S Doyle ◽

S W Hildreth ◽

P R Paradiso

Keyword(s):

Fatty Acid ◽

Respiratory Syncytial Virus ◽

Human Respiratory Syncytial Virus ◽

Fusion Glycoprotein ◽

Syncytial Virus

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Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus

Microorganisms ◽

10.3390/microorganisms9061293 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1293

Author(s):

Gaspar A. Pacheco ◽

Nicolás M. S. Gálvez ◽

Jorge A. Soto ◽

Catalina A. Andrade ◽

Alexis M. Kalergis

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A ◽

Human Respiratory Syncytial Virus ◽

Respiratory Pathogens ◽

Parainfluenza Viruses ◽

Starting Point ◽

The Social ◽

Syncytial Virus ◽

Tract Infections ◽

Polymicrobial Infections

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

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