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Respiratory syncytial virus entry and how to block it

Nature Reviews Microbiology volume 17, pages 233–245 (2019)Cite this article

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Abstract

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in young children and elderly people. Although the virus was isolated in 1955, an effective RSV vaccine has not been developed, and the only licensed intervention is passive immunoprophylaxis of high-risk infants with a humanized monoclonal antibody. During the past 5 years, however, there has been substantial progress in our understanding of the structure and function of the RSV glycoproteins and their interactions with host cell factors that mediate entry. This period has coincided with renewed interest in developing effective interventions, including the isolation of potent monoclonal antibodies and small molecules and the design of novel vaccine candidates. In this Review, we summarize the recent findings that have begun to elucidate RSV entry mechanisms, describe progress on the development of new interventions and conclude with a perspective on gaps in our knowledge that require further investigation.

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Fig. 1: Respiratory syncytial virus virion.
Fig. 2: Attachment protein structure.
Fig. 3: Fusion protein structure.
Fig. 4: Attachment and fusion.
Fig. 5: Fusion protein binding sites for antibodies and small molecules.

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Acknowledgements

The authors dedicate this Review to the memory of José A. Melero, a wonderful colleague and scientist who contributed much to the study of the RSV F and G proteins. The authors thank B. Graham, J. Langedijk and members of the McLellan laboratory for helpful comments on the manuscript, and M. Gilman for assistance with the figures.

Reviewer information

Nature Reviews Microbiology thanks L. Bont and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Michael B. Battles

  2. Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA

    Jason S. McLellan

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  1. Michael B. Battles
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  2. Jason S. McLellan
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Contributions

M.B.B. researched data for the article. M.B.B. and J.S.M. made substantial contributions to discussions of the content. M.B.B. and J.S.M. wrote the article. J.S.M. reviewed and edited the manuscript before submission.

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Correspondence to Jason S. McLellan.

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Competing interests

J.S.M. is a named inventor on patents for vaccines and/or monoclonal antibodies for RSV and coronaviruses, has received research funding from MedImmune and Janssen Pharmaceuticals, has been a paid consultant for MedImmune and is on the scientific advisory board for Calder Biosciences. M.B.B. is currently employed by Adimab.

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Glossary

Nasopharynx

The upper part of the pharynx that connects with the nasal cavity.

Bronchioles

Small tubes in the lung through which air is delivered to the alveoli.

Alveoli

Small air sacs in the lung that provide rapid gas exchange with blood.

Bronchiolitis

Inflammation of the bronchioles that reduces air passage.

Formalin

An aqueous solution of formaldehyde.

Neutrophil

Most abundant type of white blood cell.

Immune complex

An antibody bound to its antigen.

Passive immunoprophylaxis

The administration of an exogenously produced antibody given before infection occurs.

Apoptosis

Programmed cell death.

Glycoproteins

Proteins to which carbohydrates are covalently attached.

Ectodomain

The portion of a membrane protein that resides outside the cell or virion.

Cystine noose

A surface-accessible loop structure containing one or more disulfide bonds.

Serotype

A serologically distinguishable strain of a microorganism.

Protomer

A structural unit of an oligomeric protein.

Heptad repeat

A seven-amino-acid motif ‘abcdefg’ where a and d are hydrophobic.

Antigenic drift

The accumulation of amino acid substitutions that reduce antibody binding.

Apical surface

The surface of a polarized cell that faces the lumen or external environment.

Type 1 alveolar pneumocytes

Surface epithelial cells of alveoli involved in gas exchange.

Chemokine

A small secreted protein that stimulates recruitment of white blood cells.

Macropinocytosis

The nonselective uptake of extracellular molecules into endocytic vesicles.

Bronchopulmonary dysplasia

A chronic lung disease caused by mechanical ventilation and long-term oxygen use that results in damage to alveoli.

Antigenic site

A group of spatially related antibody epitopes.

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Battles, M.B., McLellan, J.S. Respiratory syncytial virus entry and how to block it. Nat Rev Microbiol 17, 233–245 (2019). https://doi.org/10.1038/s41579-019-0149-x

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