Abstract
The human cytomegalovirus (HCMV), whose genome is 235 ± 1.9 kbp long, is a common herpesvirus. However, the functions of many of its genes are still unknown. HCMV is closely associated with various human diseases and infects 60–90% of the global population. It can infect various human cells, including fibroblasts, epithelial cells, endothelial cells, smooth muscle cells, and monocytes. Although HCMV infection is generally asymptomatic and causes subtle clinical symptoms, it can generate a robust immune response and establish a latent infection in immunocompromised individuals, including those with AIDS, transplant recipients, and developing fetuses. Currently available antivirals approved for the treatment of HCMV-associated diseases are limited by dose-limiting toxicity and the emergence of resistance; however, vaccines and immunoglobulins are unavailable. In this review, we have summarized the recent literature on 43 newly identified HCMV genes. We have described their novel functions on the viral replication cycle, latency, and host immune evasion. Further, we have discussed HCMV-associated diseases and current therapeutic targets. Our review may provide a foundational basis for studies aiming to prevent and develop targeted therapies for HCMV-associated diseases.
Highlights
The human cytomegalovirus (HCMV), whose linear doublestranded DNA genome is 235 ± 1.9 kbp in length, has the largest genome among human herpesviruses. It has an E-type genome structure consisting of two large reverse domains called long (L) and short (S), each of which is composed of three regions: central unique, unique long, and unique short (Van Damme and Van Loock, 2014)
HCMV UL34 encodes a sequence-specific DNA binding protein, which interacts with pUL84, pIE2, and pUL44 and contributes to the establishment of a nuclear environment necessary for viral gene expression and DNA replication (Rana and Biegalke, 2014; Slayton et al, 2018). pUL44 is an obligate nuclear-resident, non-structural viral protein for HCMV DNA replication (Neo et al, 2019)
HCMV encodes UL94 related to systemic sclerosis (SSc), which may function in cellular gene expression and induce apoptosis in human endothelial cells (Lunardi et al, 2000)
Summary
The human cytomegalovirus (HCMV), whose linear doublestranded DNA genome is 235 ± 1.9 kbp in length, has the largest genome among human herpesviruses. Human cytomegalovirus genes are involved in diverse processes, including latency, immunomodulation, assembly, maturation, egress, viral protein, gene expression and regulation, replication, cell tropism and cell type-specific replication, modulation of the host cell cycle and protein synthesis, viral growth, cellular tracking, nucleotide repair and modification, entry, viral spread, manipulation of host cell signaling pathways, apoptosis, angiogenesis, and tumor formation (Van Damme and Van Loock, 2014; Supplementary Table S2). In terms of the virus life cycle, HCMV gene functions can be divided into entry, replication, assembly, maturation, and egress.
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