Diversity and evolution of chromatin proteins encoded by DNA viruses

Abstract

Double-stranded DNA viruses display a great variety of proteins that interact with host chromatin. Using the wealth of available genomic and functional information, we have systematically surveyed chromatin-related proteins encoded by dsDNA viruses. The distribution of viral chromatin-related proteins is primarily influenced by viral genome size and the superkingdom to which the host of the virus belongs. Smaller viruses usually encode multifunctional proteins that mediate several distinct interactions with host chromatin proteins and viral or host DNA. Larger viruses additionally encode several enzymes, which catalyze manipulations of chromosome structure, chromatin remodeling and covalent modifications of proteins and DNA. Among these viruses, it is also common to encounter transcription factors and DNA-packaging proteins such as histones and IHF/HU derived from cellular genomes, which might play a role in constituting virus-specific chromatin states. Through all size ranges a subset of domains in viral chromatin proteins appear to have been derived from those found in host proteins. Examples include the Zn-finger domains of the E6 and E7 proteins of papillomaviruses, SET-domain methyltransferases and Jumonji-related demethylases in certain nucleocytoplasmic large DNA viruses and BEN domains in poxviruses and polydnaviruses. In other cases, chromatin-interacting modules, such as the LxCxE motif, appear to have been widely disseminated across distinct viral lineages, resulting in similar retinoblastoma targeting strategies. Viruses, especially those with large linear genomes, have evolved a number of mechanisms to manipulate viral chromosomes in the process of replication-associated recombination. These include topoisomerases, Rad50/SbcC-like ABC ATPases and a novel recombinase system in bacteriophages utilizing RecA and Rad52 homologs. Larger DNA viruses also encode SWI2/SNF2 and A18-like ATPases which appear to play specialized roles in transcription and recombination. Finally, it also appears that certain domains of viral provenance have given rise to key functions in eukaryotic chromatin such as a HEH domain of chromosome tethering proteins and the TET/JBP-like cytosine and thymine hydroxylases.

Diversity of Viruses Infecting the Green Microalga Ostreococcus lucimarinus

“…Thus, manipulation of host phosphate uptake may be an important adaptation for viral proliferation in marine systems, although it is not necessarily an indicator of low ambient phosphate concentrations (10,54,58). Methyltransferase genes also are found frequently in viral genomes, where they protect the viral genome against degradation and/or might modify the host genome (59). Depending on the virus, 3 to 22 ORFs are specific to just one of the OlV genomes and are not found in other prasinoviruses sequenced to date.…”

DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway

“…Thus the viral oncogenes ability to drive unregulated cell cycle division through the LXCXE motif and the progression to cancer was simply and unintended evolutionary consequence. Interestingly, most DNA viruses that infect humans encode proteins with LXCXE motif, but only a minority of these viruses are known to cause cancer 46 , suggesting that this motif in viruses is most relevant and originally evolved for the purpose of evading a response from the host. For example, low-risk types like HPV6 can also bind Rb and possess a LXCXE motif, but cannot activate E2F for cell cycle progression into S phase.…”

Folding of a Cyclin Box

“…1), an interaction that is essential for Rb-mediated G 1 cell cycle arrest (1). Both the LXCXE and E2F clefts are targeted by viral proteins, among them the small DNA tumor virus proteins HPV E7, adenovirus E1A, and polyomavirus T antigen, highlighting their importance for virus-mediated control of the host cell cycle (27).…”