Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells

Ricemeyer, Lena; Aguilar-Hernández, Nayeli; López, Tomás; Espinosa, Rafaela; Lanning, Sarah; Mukherjee, Santanu; Cuellar, Carolina; López, Susana; Arias, Carlos F.; DuBois, Rebecca M.

doi:10.1128/jvi.01415-21

Title: Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells

Journal Article · Wed Oct 06 00:00:00 EDT 2021 · Journal of Virology

DOI:https://doi.org/10.1128/jvi.01415-21· OSTI ID:1861859

^[1]; Aguilar-Hernández, Nayeli ^[2]; López, Tomás ^[2]; Espinosa, Rafaela ^[2]; Lanning, Sarah ^[1]; Mukherjee, Santanu ^[1]; Cuellar, Carolina ^[1];

^[2];

^[1]

Univ. of California, Santa Cruz, CA (United States)
Univ. Nacional Autonoma de Mexico (UNAM) (Mexico)

Human astrovirus is an important cause of viral gastroenteritis worldwide. Young children, the elderly, and the immunocompromised are especially at risk for contracting severe disease. However, no vaccines exist to combat human astrovirus infection. Evidence points to the importance of antibodies in protecting healthy adults from reinfection. To develop an effective subunit vaccine that broadly protects against diverse astrovirus serotypes, we must understand how neutralizing antibodies target the capsid surface at the molecular level. Here, we report the structures of the human astrovirus capsid spike domain bound to two neutralizing monoclonal antibodies. These antibodies bind two distinct conformational epitopes on the spike surface. We add to existing evidence that the human astrovirus capsid spike contains a receptor-binding domain and demonstrate that both antibodies neutralize human astrovirus by blocking virus attachment to host cells. We identify patches of conserved amino acids which overlap or border the antibody epitopes and may constitute a receptor-binding site. Our findings provide a basis for developing therapies to prevent and treat human astrovirus gastroenteritis.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357

OSTI ID:: 1861859

Alternate ID(s):: OSTI ID: 1863060

Journal Information:: Journal of Virology, Vol. 96, Issue 1; ISSN 0022-538X

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Title: Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells

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