The Small Hydrophobic Protein of the Human Respiratory Syncytial Virus Forms Pentameric Ion Channels

Gan, Siok-Wan; Tan, Edward; Lin, Xiangmin; Yu, Dejie; Wang, Juejin; Tan, Gregory Ming-Yeong; Vararattanavech, Ardcharaporn; Yeo, Chiew Ying; Soon, Cin Huang; Soong, Tuck Wah; Pervushin, Konstantin; Torres, Jaume

doi:10.1074/jbc.m111.332791

Cited by 127 publications

(149 citation statements)

References 71 publications

(101 reference statements)

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

Section: Other Rna Virus Viroporinsmentioning

confidence: 99%

“…SH is commonly thought to form pentameric oligomers (Collins & Mottet, 1993;Gan et al, 2008Gan et al, , 2012, although hexamers have also been reported (Carter et al, 2010). Solution NMR structures have been reported for the pentameric bundles, yet have not been added to the PDB (Gan et al, 2008(Gan et al, , 2012. Both SH TMD peptides and full-length protein form cation-selective channels in vitro (Gan et al, 2008), as well as promoting bacterial membrane permeability (Perez et al, 1997) and mediating dye release from liposomes (Carter et al, 2010).…”

Section: Other Rna Virus Viroporinsmentioning

confidence: 99%

“…The effect of low pH upon channel opening appears to be context dependent, with conserved His22, His51 and Trp15 residues implicated in channel gating/opening. However, deletion of both His residues is required to generate non-functional channels and it remains unclear as to the precise effect of pH upon channel opening (Gan et al, 2008(Gan et al, , 2012. Recently, pyronin B was identified as an inhibitor of SH activity in liposome dye-release assays, suspended bilayers and RSV spread in culture .…”

Section: Other Rna Virus Viroporinsmentioning

confidence: 99%

See 2 more Smart Citations

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

124

146

View full text Add to dashboard Cite

The channel-forming activity of a family of small, hydrophobic integral membrane proteins termed 'viroporins' is essential to the life cycles of an increasingly diverse range of RNA and DNA viruses, generating significant interest in targeting these proteins for antiviral development. Viroporins vary greatly in terms of their atomic structure and can perform multiple functions during the virus life cycle, including those distinct from their role as oligomeric membrane channels. Recent progress has seen an explosion in both the identification and understanding of many such proteins encoded by highly significant pathogens, yet the prototypic M2 proton channel of influenza A virus remains the only example of a viroporin with provenance as an antiviral drug target. This review attempts to summarize our current understanding of the channel-forming functions for key members of this growing family, including recent progress in structural studies and drug discovery research, as well as novel insights into the life cycles of many viruses revealed by a requirement for viroporin activity. Ultimately, given the successes of drugs targeting ion channels in other areas of medicine, unlocking the therapeutic potential of viroporins represents a valuable goal for many of the most significant viral challenges to human and animal health.

show abstract

Section: Other Rna Virus Viroporinsmentioning

confidence: 99%

Section: Other Rna Virus Viroporinsmentioning

confidence: 99%

Section: Other Rna Virus Viroporinsmentioning

confidence: 99%

See 1 more Smart Citation

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

124

146

View full text Add to dashboard Cite

show abstract

“…117 HRSV small hydrophobic (SH) protein: it is thought that this protein works as an important viroporin during hRSV pathogenesis. 118 This protein also inhibits apoptosis in order to promote viral replication, as recombinant hRSV lacking the SH protein induced a significant cytopathic effect in different cell lines, compare with WT hRSV. 119 In addition, the hRSV SH has been shown to inhibit the NF-kb pathway through a decrease in the TNF-a production in mouse fibroblastic cells.…”

Section: Role Of Hrsv Proteins In Immunomodulationmentioning

confidence: 99%

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

et al. 2016

View full text Add to dashboard Cite

Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections.In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.

show abstract

“…SH is a small hydrophobic protein whose function is still unclear and is incorporated in low amounts into the virus particle (Bao et al , 2008; Gan et al , 2012). G is a heavily glycosylated and highly variable type II glycoprotein that resembles mucins and serves as the viral attachment protein (Levine et al , 1987; Thammawat et al , 2008).…”

Section: Introductionmentioning

confidence: 99%

Chimeric Pneumoviridae fusion proteins as immunogens to induce cross‐neutralizing antibody responses

et al. 2017

View full text Add to dashboard Cite

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV. However, no cross‐neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well‐characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus‐specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross‐neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross‐neutralizing antibody and protective responses against more than one human pneumovirus.

show abstract

The Small Hydrophobic Protein of the Human Respiratory Syncytial Virus Forms Pentameric Ion Channels

Cited by 127 publications

References 71 publications

Viroporins: structure, function and potential as antiviral targets

Viroporins: structure, function and potential as antiviral targets

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

Chimeric Pneumoviridae fusion proteins as immunogens to induce cross‐neutralizing antibody responses

Contact Info

Product

Resources

About