PH-induced conformational changes of human bocavirus capsids

Mengxiao Luo, Mario Mietzsch, Paul Chipman, Kangkang Song, Chen Xu, John Spear, Duncan Sousa, Robert McKenna, Maria Söderlund-Venermo, Mavis Agbandje-McKenna

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Human bocavirus 1 (HBoV1) and HBoV2 to -4 infect children and immunocompromised individuals, resulting in respiratory and gastrointestinal infections, respectively. Using cryo-electron microscopy and image reconstruction, the HBoV2 capsid structure was determined to 2.7-Å resolution at pH 7.4 and compared to the previously determined HBoV1, HBoV3, and HBoV4 structures. Consistent with previous findings, surface variable region III (VR-III) of the capsid protein VP3, proposed as a host tissue tropism determinant, was structurally similar among the gastrointestinal strains HBoV2 to -4, but differed from that of HBoV1 with its tropism for the respiratory tract. Toward understanding the entry and trafficking properties of these viruses, HBoV1 and HBoV2 were further analyzed as species representatives of the two HBoV tropisms. Their cell surface glycan-binding characteristics were analyzed, and capsid structures determined to 2.5- to 2.7-Å resolution at pHs 5.5 and 2.6, conditions normally encountered during infection. The data showed that glycans with terminal sialic acid, galactose, GlcNAc, or heparan sulfate moieties do not facilitate HBoV1 or HBoV2 cellular attachment. With respect to trafficking, conformational changes common to both viruses were observed under low-pH conditions localized to the VP N terminus under the 5-fold channel, in the surface loops VR-I and VR-V and specific side chain residues such as cysteines and histidines. The 5-fold conformational movements provide insight into the potential mechanism of VP N-terminal dynamics during HBoV infection, and side chain modifications highlight pH-sensitive regions of the capsid.

Original languageEnglish (US)
Article numbere02329
JournalJournal of virology
Volume95
Issue number8
DOIs
StatePublished - Apr 2021
Externally publishedYes

Keywords

  • Capsid structure
  • Cryo-electron microscopy
  • Cysteine modifications
  • HBoV2
  • Histidine modifications
  • Human bocavirus
  • Low-pH conditions
  • Parvovirus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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