Respiratory Syncytial Virus G Protein and G Protein CX3C Motif Adversely Affect CX3CR1+ T Cell Responses

Harcourt, Jennifer L.; Alvarez, Rene; Jones, Les; Henderson, Christine; Anderson, Larry J.; Tripp, Ralph A.

doi:10.4049/jimmunol.176.3.1600

Cited by 130 publications

(140 citation statements)

References 50 publications

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“…interaction with the fractalkine receptor, CX3CR1, a key mediator of cell trafficking to the infected lung (15,21). Consistent with these findings, human polymorphisms showing reduced activity of either TLR4 (27) or CX3CR1 (28) were significantly overrepresented in studies of infants with severe RSV disease.…”

supporting

confidence: 73%

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Collarini

Lee

Foord

et al. 2009

The Journal of Immunology

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111

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Native human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality Abs has posed a barrier to discovery. Using a novel single-cell phenotyping technology, we have overcome this barrier to discover human Abs targeting the conserved but poorly immunogenic central motif of respiratory syncytial virus (RSV) G protein. For the entire cohort of 24 subjects with recent RSV infection, B cells producing Abs meeting these stringent specificity criteria were rare, <10 per million. Several of the newly cloned Abs bind to the RSV G protein central conserved motif with very high affinity (Kd 1–24 pM). Two of the Abs were characterized in detail and compared with palivizumab, a humanized mAb against the RSV F protein. Relative to palivizumab, the anti-G Abs showed improved viral neutralization potency in vitro and enhanced reduction of infectious virus in a prophylaxis mouse model. Furthermore, in a mouse model for postinfection treatment, both anti-G Abs were significantly more effective than palivizumab at reducing viral load. The combination of activity in mouse models for both prophylaxis and treatment makes these high-affinity human-derived Abs promising candidates for human clinical testing.

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supporting

confidence: 73%

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Collarini

Lee

Foord

et al. 2009

The Journal of Immunology

Self Cite

111

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“…However, the conserved cysteine-rich region of the G protein has homology with the fourth domain of the TNF receptor [80] and may inhibit components of the innate response by binding to TNFα or an unknown TNF homologue. Studies with rHRSV lacking the cysteine-rich region of the G protein suggest that although this region is not required for efficient viral replication in mice [139], it may play a role in suppressing the anti-viral T-cell response [56]. As mentioned previously, field isolates of BRSV have been identified that lack one or more of the cysteines in the central conserved region (see Sect.…”

Section: The Role Of the G Protein In The Pathogenesis Of Brsvmentioning

confidence: 99%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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-Bovine respiratory syncytial virus (BRSV) belongs to the pneumovirus genus within the family Paramyxoviridae and is a major cause of respiratory disease in young calves. BRSV is enveloped and contains a negative sense, single-stranded RNA genome encoding 11 proteins. The virus replicates predominantly in ciliated respiratory epithelial cells but also in type II pneumocytes. It appears to cause little or no cytopathology in ciliated epithelial cell cultures in vitro, suggesting that much of the pathology is due to the host's response to virus infection. RSV infection induces an array of pro-inflammatory chemokines and cytokines that recruit neutrophils, macrophages and lymphocytes to the respiratory tract resulting in respiratory disease. Although the mechanisms responsible for induction of these chemokines and cytokines are unclear, studies on the closely related human (H)RSV suggest that activation of NF-κB via TLR4 and TLR3 signalling pathways is involved. An understanding of the mechanisms by which BRSV is able to establish infection and induce an inflammatory response has been facilitated by advances in reverse genetics, which have enabled manipulation of the virus genome. These studies have demonstrated an important role for the non-structural proteins in anti-interferon activity, a role for a virokinin, released during proteolytic cleavage of the fusion protein, in the inflammatory response and a role for the SH and the secreted form of the G protein in establishing pulmonary infection. Knowledge gained from these studies has also provided the opportunity to develop safe, stable, live attenuated virus vaccine candidates.

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“…Moreover, the secreted form of the G protein has a chemokine-like motif (CX3C) that competes with fractalkine (CX3CL1) in binding to its receptor CX3CR1, thus reducing the CX3CR1 C T cells response. 116 HRSV Fusion (F) protein: this viral protein is required for the fusion of viral particle with the host cells 4 and also play a direct role in the ability of hRSV to decrease the proliferation of these cells by contact. 117 In fact, when Vero cells express the F protein or are infected with a version of hRSV that only have F protein on its surface, they reduce the proliferation and response to mitogen stimulus.…”

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

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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.

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Respiratory Syncytial Virus G Protein and G Protein CX3C Motif Adversely Affect CX3CR1+ T Cell Responses

Cited by 130 publications

References 50 publications

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Bovine respiratory syncytial virus infection

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

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