Immunopathology of RSV: An Updated Review

Bergeron, Harrison C.; Tripp, Ralph A.

doi:10.3390/v13122478

Cited by 50 publications

(68 citation statements)

References 353 publications

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“…A minor IL-10 response was detected for PBMCs from subjects immunized with 5×10 4 CFU of rBCG-N-hRSV. These results suggest that immunization with either 5×10 3 or 5×10 4 CFU of rBCG-N-hRSV led to the secretion of pro-inflammatory cytokines typically associated with immune responses against intracellular pathogens, such as viruses and mycobacteria [16]–[19]. Moreover, the modest increase in IL-10 concentration is indicative of a balanced immune response [20].…”

Section: Resultsmentioning

confidence: 99%

A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

Pacheco

Gálvez

Andrade

et al. 2022

Preprint

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BACKGROUND: The human respiratory syncytial virus (hRSV) is a respiratory pathogen responsible for most cases of acute lower respiratory tract infections in infants worldwide. Although this virus represents a significant social and economic burden, there are no safe and effective available vaccines. rBCG-N-hRSV is a vaccine candidate consisting of a recombinant attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) expressing the nucleoprotein of hRSV (N-hRSV). METHODS: rBCG-N-hRSV was applied intradermally in three different doses (5x103, 5x104, or 1x105 CFU) to healthy adults enrolled in a randomized, double-blind, dose-escalating phase 1 clinical trial (NCT03213405). Blood samples were taken before and at various time points after immunization. Cellular and humoral immune parameters were assessed by analyzing circulating immune cells and sera, respectively. RESULTS: Perforin- and Granzyme B-producing PBMCs recognizing viral or mycobacterial antigens were found to increase after immunization with rBCG-N-hRSV. These cells also upregulated IFN-g; and IL-10 secretion in response to N-hRSV and upregulated IFNg, IL-6, and TNF-a; secretion in response to mycobacterial proteins. While naive T cell populations contracted over time, no specific memory T cell subset expanded significantly. Although binding to C1q by anti-N-hRSV or anti-mycobacterial antibodies decreased slightly after immunization, no apparent changes were found in the concentration of IgG subclasses against N-hRSV or mycobacterial antigens. CONCLUSIONS: The immune response elicited by immunization with rBCG-N-hRSV consists mainly of antigen-specific T cells. The data reported here provide novel information about the characteristics of the immune response elicited after immunization with rBCG-N-hRSV, supporting the safety and immunogenicity of this vaccine.

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Section: Resultsmentioning

confidence: 99%

A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

Pacheco

Gálvez

Andrade

et al. 2022

Preprint

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“…Although vaccines are available for CoV2 and flu, there is a paucity of effective antiviral drugs. For RSV, there is no vaccine available, and therapeutic treatments are very limited [ 24 , 25 ]. Moreover, there are few preventive or therapeutic interventions available for respiratory viruses.…”

Section: Respiratory Virusesmentioning

confidence: 99%

Repurposing Probenecid to Inhibit SARS-CoV-2, Influenza Virus, and Respiratory Syncytial Virus (RSV) Replication

Tripp

Martin²

2022

Viruses

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Viral replication and transmissibility are the principal causes of endemic and pandemic disease threats. There remains a need for broad-spectrum antiviral agents. The most common respiratory viruses are endemic agents such as coronaviruses, respiratory syncytial viruses, and influenza viruses. Although vaccines are available for SARS-CoV-2 and some influenza viruses, there is a paucity of effective antiviral drugs, while for RSV there is no vaccine available, and therapeutic treatments are very limited. We have previously shown that probenecid is safe and effective in limiting influenza A virus replication and SARS-CoV-2 replication, along with strong evidence showing inhibition of RSV replication in vitro and in vivo. This review article will describe the antiviral activity profile of probenecid against these three viruses.

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“…In this work, we aimed to obtain a general picture of chaperones utilized by a medically relevant human RNA virus, respiratory syncytial virus (RSV). RSV is among the most important respiratory infections in the pediatric setting and causes significant morbidity in the elderly population ( Griffiths et al, 2017 ; Bergeron and Tripp, 2021 ). RSV belongs to the Mononegavirales order, harboring a single-stranded, negative-sense RNA genome, and encodes 11 different proteins.…”

Section: Introductionmentioning

confidence: 99%

Identification of Cytoplasmic Chaperone Networks Relevant for Respiratory Syncytial Virus Replication

Latorre

Geller

2022

Front. Microbiol.

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RNA viruses have limited coding capacity and must therefore successfully subvert cellular processes to facilitate their replication. A fundamental challenge faced by both viruses and their hosts is the ability to achieve the correct folding and assembly of their proteome while avoiding misfolding and aggregation. In cells, this process is facilitated by numerous chaperone systems together with a large number of co-chaperones. In this work, we set out to define the chaperones and co-chaperones involved in the replication of respiratory syncytial virus (RSV). Using an RNAi screen, we identify multiple members of cellular protein folding networks whose knockdown alters RSV replication. The reduced number of chaperones and co-chaperones identified in this work can facilitate the unmasking of specific chaperone subnetworks required for distinct steps of the RSV life cycle and identifies new potential targets for antiviral therapy. Indeed, we show that the pharmacological inhibition of one of the genes identified in the RNAi screen, valosin-containing protein (VCP/p97), can impede the replication of RSV by interfering with the infection cycle at multiple steps.

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Immunopathology of RSV: An Updated Review

Cited by 50 publications

References 353 publications

A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

Repurposing Probenecid to Inhibit SARS-CoV-2, Influenza Virus, and Respiratory Syncytial Virus (RSV) Replication

Identification of Cytoplasmic Chaperone Networks Relevant for Respiratory Syncytial Virus Replication

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