Structural Aspects of Betaherpesvirus-Encoded Proteins

Nishimura, Mitsuhiro; Mori, Yasuko

doi:10.1007/978-981-10-7230-7_11

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“…The elongated arrangement of the gQ1/gQ2 in the tetramer is reminiscent of the HCMV pentamer in which the UL128/UL130/UL131 part docks on the gH/gL, extending the longitudinal axis [26,37]. The HCMV pentamer (gH/gL/UL128/UL130/UL131) and the trimer (gH/gL/gO) are located at the associated UL128/UL130/UL131 or gO on the top of gL [37], whereas the EBV gH/gL/gp42 complex does not place the gp42 on gL, but the gp42 almost exclusively interacts with the gH apart from the gL [25,33,34,38]. Thus, the gQ1/gQ2 arrangement unveiled by our present analyses might indicate a shared feature among the viral ligands of betaherpesviruses.…”

Section: The Tetramer's Structurementioning

confidence: 99%

Structural basis for the interaction of human herpesvirus 6B tetrameric glycoprotein complex with the cellular receptor, human CD134

et al. 2020

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A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (K D = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A singleparticle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint.

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