From recognition to execution — the HCMV Pentamer from receptor binding to fusion triggering

Malito, E.; Chandramouli, Sumana; Carfı́, Andrea

doi:10.1016/j.coviro.2018.05.004

Cited by 20 publications

(21 citation statements)

References 51 publications

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“…Only two glycoproteins, US11 and UL55 (glycoprotein B, gB) were among selection targets on the HCMV branch. gB mediates viral-host cell fusion and is a major target antigen [24]. Mapping of positively selected codons relative to known antigenic domains (AD) indicated that two of the three selected sites are located within ADs that elicit neutralizing antibodies [25,26] (Fig 2C).…”

Section: Adaptive Evolution In the Hcmv Lineagementioning

confidence: 99%

Past and ongoing adaptation of human cytomegalovirus to its host

et al. 2020

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Cytomegaloviruses (order Herpesvirales) display remarkable species-specificity as a result of long-term co-evolution with their mammalian hosts. Human cytomegalovirus (HCMV) is exquisitely adapted to our species and displays high genetic diversity. We leveraged information on inter-species divergence of primate-infecting cytomegaloviruses and intra-species diversity of clinical isolates to provide a genome-wide picture of HCMV adaptation across different time-frames. During adaptation to the human host, core viral genes were commonly targeted by positive selection. Functional characterization of adaptive mutations in the primase gene (UL70) indicated that selection favored amino acid replacements that decrease viral replication in human fibroblasts, suggesting evolution towards viral temperance. HCMV intra-species diversity was largely governed by immune system-driven selective pressure, with several adaptive variants located in antigenic domains. A significant excess of positively selected sites was also detected in the signal peptides (SPs) of viral proteins, indicating that, although they are removed from mature proteins, SPs can contribute to viral adaptation. Functional characterization of one of these SPs indicated that adaptive variants modulate the timing of cleavage by the signal peptidase and the dynamics of glycoprotein intracellular trafficking. We thus used evolutionary information to generate experimentally-testable hypotheses on the functional effect of HCMV genetic diversity and we define modulators of viral phenotypes.

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Section: Adaptive Evolution In the Hcmv Lineagementioning

confidence: 99%

Past and ongoing adaptation of human cytomegalovirus to its host

et al. 2020

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“…This protein is a component of a pentameric envelope protein complex, consisting of glycoproteins H and L, as well as pUL130 and pUL131 [58]. The pentameric complex (PC) has been shown to be important for HCMV infection of cell types such as endothelial cells and epithelial cells [58][59][60][61]. Laboratory HCMV strains are devoid of the PC because of mutations in the UL128-131 gene region.…”

Section: Ms-based Characterization Of the Hcmv Virion Proteomementioning

confidence: 99%

Mass Spectrometry-Based Characterization of the Virion Proteome, Phosphoproteome, and Associated Kinase Activity of Human Cytomegalovirus

et al. 2020

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The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. Currently, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remain elusive. Protein phosphorylation is a key regulator determining the sequential changes in the conformation, binding, dynamics, and stability of proteins in the course of multiprotein assembly. In this review, we present a comprehensive map of the HCMV virion proteome, including a refined view on the virion phosphoproteome, based on previous publications supplemented by new results. Thus, a novel dataset of viral and cellular proteins contained in HCMV virions is generated, providing a basis for future analyses of individual phosphorylation steps and sites involved in the orchestrated assembly of HCMV virion-specific multiprotein complexes. Finally, we present the current knowledge on the activity of pUL97, the HCMV-encoded and virion-associated kinase, in phosphorylating viral and host proteins.

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“…Among the core genes, we found evidence of episodic positive selection for three glycoproteins: gB (UL27), gH (UL22) and gM (UL10) (Figure 2 and Figure S1). UL27 encodes the viral envelope glycoprotein B (gB), which is a major target antigen in herpesviruses (Malito et al, 2018). Both selected sites in gB are located in the ectodomain ( Figure 2) and one of them, A334, is part of an epitope recognized by the SS55 neutralizing antibody (Cairns et al, 2014) (Figure 2).…”

Section: Adaptive Evolution In the Hominin-infecting Simplexvirus Linmentioning

confidence: 99%

Simplexviruses successfully adapt to their host by fine-tuning immune responses

Mozzi

Cagliani

Pontremoli

et al. 2020

Preprint

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Primate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants. Positively selected non-core proteins were involved in different immune-escape mechanisms. By expressing mutants of one of these proteins (ICP47), we show that the amino acid status at the positively selected sites is sufficient to induce HLA-G. HSV-1/HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. Thus, the evolution of ICP47 in HSV-1/HSV-2 determined the loss of an immunosuppressive effect, suggesting that simplexviruses tune immune responses to promote successful co-existence with their hosts. These results also help explain the high pathogenicity of B virus in humans.

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From recognition to execution — the HCMV Pentamer from receptor binding to fusion triggering

Cited by 20 publications

References 51 publications

Past and ongoing adaptation of human cytomegalovirus to its host

Past and ongoing adaptation of human cytomegalovirus to its host

Mass Spectrometry-Based Characterization of the Virion Proteome, Phosphoproteome, and Associated Kinase Activity of Human Cytomegalovirus

Simplexviruses successfully adapt to their host by fine-tuning immune responses

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