TY - JOUR
T1 - PH-induced conformational changes of human bocavirus capsids
AU - Luo, Mengxiao
AU - Mietzsch, Mario
AU - Chipman, Paul
AU - Song, Kangkang
AU - Xu, Chen
AU - Spear, John
AU - Sousa, Duncan
AU - McKenna, Robert
AU - Söderlund-Venermo, Maria
AU - Agbandje-McKenna, Mavis
N1 - Funding Information:
This data collection was made possible by NIH grants S10 OD018142-01 (purchase of a direct electron camera for the Titan-Krios at FSU [P. I. Taylor]), S10 RR025080-01 (purchase of an FEI Titan Krios for 3D EM [P. I. Taylor]), and U24 GM116788 (The Southeastern Consortium for Microscopy of MacroMolecular Machines [P. I. Taylor]). We thank the University of Massachusetts Medical School Cryo-EM Center, funded by the Massachusetts Life Sciences Center and the Howard Hughes Medical Institute. The Titan Krios was acquired through funds from a capital grant through Massachusetts Life Sciences Center's Competitive Capital Program and by an HHMI Transformative Technology (TT16) Award. The Sigrid Jusélius Foundation and the Life and Health.
Funding Information:
This data collection was made possible by NIH grants S10 OD018142-01 (purchase of a direct electron camera for the Titan-Krios at FSU [P. I. Taylor]), S10 RR025080-01 (purchase of an FEI Titan Krios for 3D EM [P. I. Taylor]), and U24 GM116788 (The Southeastern Consortium for Microscopy of MacroMolecular Machines [P. I. Taylor]). We thank the University of Massachusetts Medical School Cryo-EM Center, funded by the Massachusetts Life Sciences Center and the Howard Hughes Medical Institute. The Titan Krios was acquired through funds from a capital grant through Massachusetts Life Sciences Center's Competitive Capital Program and by an HHMI Transformative Technology (TT16) Award. The Sigrid Jusélius Foundation and the Life and Health
Publisher Copyright:
Copyright © 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Capsid structure
KW - Cryo-electron microscopy
KW - Cysteine modifications
KW - HBoV2
KW - Histidine modifications
KW - Human bocavirus
KW - Low-pH conditions
KW - Parvovirus
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U2 - 10.1128/JVI.02329-20
DO - 10.1128/JVI.02329-20
M3 - Article
C2 - 33472934
AN - SCOPUS:85104105659
SN - 0022-538X
VL - 95
JO - Journal of Virology
JF - Journal of Virology
IS - 8
M1 - e02329
ER -