A Unique Role of the Human Cytomegalovirus Small Capsid Protein in Capsid Assembly

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous pathogen causing life-threatening disease in immunocompromised individuals. Virus-specific processes such as capsid assembly and genome packaging can be exploited to design new antiviral strategies.

CMV-induced Hearing Loss

“…Cytomegalovirus capsid has four parts-major capsid protein (MCP), triplex dimer (Tri2), triplex monomer (Tri1), and the small capsid protein (SCP). 25 Cytomegalovirus capsids have an icosahedral structure with major capsid protein (MCP) being organized in to 150 hexons and 11 penton vertices 26…”

“…123 When both CMV IgG and A change to a worse or better hearing threshold between consecutive assessments: an absolute difference of ≥20 dB in ≥1 frequencies, ≥10 dB across any 2 or 3 adjacent frequencies, ≥10 dB in the average of the pure-tone thresholds at 0.5, 1, 2, and 4 kHz (4-frequency average), or a change from "hearing" to "no response" or vice versa at three adjacent frequencies. 116,120 Improvement of hearing loss Defined as a final threshold that is better by 10 dB or more compared with the initial threshold 26…”

Structure-Guided Mutagenesis Targeting Interactions between pp150 Tegument Protein and Small Capsid Protein Identify Five Lethal and Two Live Attenuated HCMV Mutants

“…360 triplex protein complexes (Tri), each composed of one Tri1 and two Tri2 (Tri2A & Tri2B) copies, decorate the exterior of the MCP shell, riveting neighboring MCPs together, while small capsid protein (SCP) molecules tip each MCP tower (Figure 1A). SCP, which varies from 8kDa in HCMV and 15 kDa in KSHV, has the greatest structural and sequence variability amongst herpesviruses (Close et al, 2018;Dai et al, 2015), being dispensable among both a-and g-herpesviruses but not b-herpesviruses (Borst et al, 2022;Dai et al, 2013).…”