Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome

Abstract

CMV is a major cause of morbidity and mortality in immunocompromised individuals that will benefit from the availability of a vaccine. Despite the efforts made during the last decade, no CMV vaccine is available. An ideal CMV vaccine should elicit a broad immune response against multiple viral antigens including proteins involved in virus-cell interaction and entry. However, the therapeutic use of neutralizing antibodies targeting glycoproteins involved in viral entry achieved only partial protection against infection. In this scenario, a better understanding of the CMV proteome potentially involved in viral entry may provide novel candidates to include in new potential vaccine design. In this study, we aimed to explore the CMV genome to identify proteins with putative transmembrane domains to identify new potential viral envelope proteins. We have performed in silico analysis using the genome sequences of nine different CMV strains to predict the transmembrane domains of the encoded proteins. We have identified 77 proteins with transmembrane domains, 39 of which were present in all the strains and were highly conserved. Among the core proteins, 17 of them such as UL10, UL139 or US33A have no ascribed function and may be good candidates for further mechanistic studies.

A systematic investigation into the non-genetic and genetic factors affecting the human anti-viral antibody repertoire

“…The most significant targets included RL12, UL32 (Tegument protein pp150) and UL139. Protein structure predictions have suggested that UL139 is involved in cell adhesion and could be a good target for an anti-CMV vaccine 38 , supported by our results.…”

CMV-induced Hearing Loss

“…3 The capsid surrounds and encloses the viral dsDNA genome (forming a nucleocapsid) and can be seen as an electron-dense structure in electron micrographs Protein core There are 39 core proteins, which are present in all strains and are highly conserved. 27 Among the core proteins, some are involved in cell entry and immunomodulation/immunoevasion; while the function of 17 of them (UL10, UL139 or US33A) has not been determined Enzymes Cytomegalovirus has an essential, maturational serine protease whose catalytic domain, assembling (28 kDa), is released by self-cleavage from a 74-kDa precursor (pPR, pUL80a) 28…”

An Update on Current Antiviral Strategies to Combat Human Cytomegalovirus Infection

“…The virus contains a double-stranded DNA genome of approximately 235 kbp, and it encodes numerous functional proteins, microRNAs, longnon coding RNAs and small peptides [3]. The HCMV genome contains >200 predicted open reading frames, with 71-77 proteins identified by mass spectrometry and in silico analysis [12][13][14]. Additionally, it also ex-presses four major non-coding RNAs (lncRNAs) along with at least 16 pre-miRNAs and 26 mature miRNAs [15].…”