Comparative Genomics of Herpesviridae Family to Look for Potential Signatures of Human Infecting Strains

Abstract

Herpesviridae family is one of the significant viral families which comprises major pathogens of a wide range of hosts. This family includes at least eight species of viruses which are known to infect humans. This family has evolved 180-220 million years ago and the present study highlights that it is still evolving and more genes can be added to the repertoire of this family. In addition, its core-genome includes important viral proteins including glycoprotein B and helicase. Most of the infections caused by human herpesviruses have no definitive cure; thus, search for new therapeutic strategies is necessary. The present study finds core-genome of human herpesviruses that differs from that of Herpesviridae family and nonhuman herpes strains of this family and might be a putative target for vaccine development. The phylogenetic reconstruction based upon the protein sequences of core gene set of Herpesviridae family reveals the sharp splits of its different subfamilies and supports the hypothesis of coevolution of viruses with their hosts. In addition, data mining for cis-elements in the genomes of human herpesviruses results in the prediction of numerous regulatory elements which can be used for regulating the expression of viral based vectors implicated in gene therapies.

Figure 1

Plot of the estimation of pan- and core-genome sizes of Herpesviridae family fitted with Tettelin function. (a) Pan-genome and (b) Core-genome estimates are shown after using ten random samples of the 64 taxa. Residual standard errors are reported on the right margin as a measure of the goodness of fit.

Figure 2

Venn diagrams of core-genomes generated by the BDBH, COG, and OMCL strategies for (a) 64 members of Herpesviridae family, (b) 10 HHVs of Herpesviridae family, and (c) 54 Non-HHVs of Herpesviridae family.

Figure 3

Phylogenetic tree based on the core gene set of Herpesviridae family. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (1000 replicates) are shown next to the branches.

Figure 4

Bar-plots of count of different cis-elements in the genomes of HHVs. HHV-1_17: human herpesvirus 1; HHV-2_HG52: herpes simplex virus type 2 strain HG52; HHV-3_Dumas: human herpesvirus 3 strain Dumas; HHV-4: human herpesvirus 4; HHV-4_2: human herpesvirus 4 strain AG876; HHV-5_Merlin: human herpesvirus 5 strain Merlin; HHV-6A: human herpesvirus 6A; HHV-6B_Z29: human herpesvirus 6B strain Z29; HHV-7_RK: human herpesvirus 7 strain RK; HHV-8_GK18: human herpesvirus 8 strain GK18.