Evolution and Genetic Diversity of Primate Cytomegaloviruses

Abstract

Cytomegaloviruses (CMVs) infect many mammals, including humans and non–human primates (NHPs). Human cytomegalovirus (HCMV) is an important opportunistic pathogen among immunocompromised patients and represents the most common infectious cause of birth defects. HCMV possesses a large genome and very high genetic diversity. NHP–infecting CMVs share with HCMV a similar genomic organization and coding content, as well as the course of viral infection. Recent technological advances have allowed the sequencing of several HCMV strains from clinical samples and provided insight into the diversity of NHP–infecting CMVs. The emerging picture indicates that, with the exclusion of core genes (genes that have orthologs in all herpesviruses), CMV genomes are relatively plastic and diverse in terms of gene content, both at the inter– and at the intra–species level. Such variability most likely underlies the strict species–specificity of these viruses, as well as their ability to persist lifelong and with relatively little damage to their hosts. However, core genes, despite their strong conservation, also represented a target of adaptive evolution and subtle changes in their coding sequence contributed to CMV adaptation to different hosts. Indubitably, important knowledge gaps remain, the most relevant of which concerns the role of viral genetics in HCMV–associated human disease.

Highly Conserved Interaction Profiles between Clinically Relevant Mutants of the Cytomegalovirus CDK-like Kinase pUL97 and Human Cyclins: Functional Significance of Cyclin H

“…Recently, several studies have reported on HCMV sequence information derived from comprehensive analyses using clinically relevant HCMVs as well as reference and laboratory strains [ 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. In order to collect more information about strain sequence variation of isolates in our present study, we performed viral whole genome sequencing (WGS) and comparative analysis of clinical isolates of HCMV.…”

Hematopoietic stem cells and betaherpesvirus latency

“…Herpesvirus infection, in particular, is a common concern during hematopoietic cell (and solid organ) transplant, where immunosuppression provides a cellular environment promoting viral infection and/or reactivation, which in turn can lead to additional myelosuppression, which can ultimately result in graft failure ( Ivana et al., 2022 ). Yet, while many mammalian species, from elephants to mice, are infected with herpesviruses, the evolutionary differences that prevent cross-infection, even between highly related primate betaherpesvirus species, highlight specific adaptations to the host immune system and distinct mechanisms of viral behavior ( Cagliani et al., 2020 ; Fisher and Lloyd, 2020 ). Understanding these mechanisms will provide novel insights into viral infection (and treatment), immune function, and hematopoietic mechanisms.…”

Molecular genetic and clinical aspects of socially relevant viruses underlying congenital diseases

“…Таким образом, геномы ЦМВ относительно пластичны и разнообразны с точки зрения содержания генов как на межвидовом, так и на внутривидовом уровне. Такая генетическая изменчивость в сочетании с иммунологической мимикрией, скорее всего, является ключевым элементом, лежащим в основе строгой видовой специфичности этих вирусов, а также их способности сохраняться на протяжении всей жизни с минимальными клиническими проявлениями [27]. В то же время при сравнении геномных последовательностей штаммов ЦМВ становится очевидным чрезвычайно высокий уровень их вариабельности, что объясняет сложность создания анти-ЦМВ-вакцины.…”