African Great Apes Are Naturally Infected with Roseoloviruses Closely Related to Human Herpesvirus 7

Abstract

Primates are naturally infected with herpesviruses. During the last 15 years, the search for homologues of human herpesviruses in nonhuman primates allowed the identification of numerous viruses belonging to the different herpesvirus subfamilies and genera. No simian homologue of human herpesvirus 7 (HHV7) has been reported to date. To investigate the putative existence of HHV7-like viruses in African great apes, we applied the consensus-degenerate hybrid oligonucleotide primers (CODEHOP) program-mediated PCR strategy to blood DNA samples from the four common chimpanzee subspecies (Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii), pygmy chimpanzees (Pan paniscus), as well as lowland gorillas (Gorilla gorilla gorilla). This study led to the discovery of a novel roseolovirus close to HHV7 in each of these nonhuman primate species and subspecies. Generation of the partial glycoprotein B (1,111-bp) and full-length DNA polymerase (3,036/3,042-bp) gene sequences allowed the deciphering of their evolutionary relationships. Phylogenetic analyses revealed that HHV7 and its African great ape homologues formed well-supported monophyletic lineages whose topological resemblance to the host phylogeny is suggestive of virus-host codivergence. Notably, the evolutionary branching points that separate HHV7 from African great ape herpesvirus 7 are remarkably congruent with the dates of divergence of their hosts. Our study shows that African great apes are hosts of human herpesvirus homologues, including HHV7 homologues, and that the latter, like other DNA viruses that establish persistent infections, have cospeciated with their hosts. IMPORTANCEHuman herpesviruses are known to possess simian homologues. However, surprisingly, none has been identified to date for human herpesvirus 7 (HHV7). This study is the first to describe simian homologues of HHV7. The extensive search performed on almost all African great ape species and subspecies, i.e., common chimpanzees of the four subspecies, bonobos, and lowland gorillas, has allowed characterization of a specific virus in each. Genetic characterization of the partial glycoprotein B and fulllength DNA polymerase gene sequences, followed by their phylogenetic analysis and estimation of divergence times, has shed light on the evolutionary relationships of these viruses. In this respect, we conclusively demonstrate the cospeciation between these new viruses and their hosts and report cases of cross-species transmission between two common chimpanzee subspecies in both directions.

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

“…The prevalence of CiHHV-6A in continental Europe as shown in the meta-analysis may point to early germline integration of the virus genomes and spread in populations emigrating from Africa. This is consistent with the host co-evolutionary hypothesis for herpesvirus [ 46 , 69 , 70 ] which would place HHV-6A and HHV-6B divergence after common ancestors represented at nodes distinct to related chimpanzee HHV-6-like roseolovirus (see gb AY359407 and gb AY854171) as described [ 71 ]. Following the co-evolution model this would also place the ancestral node for HHV-6A and HHV-6B after the divergence of humans from chimpanzees (between two and six million years ago).…”

Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

“…The status of MneHV7 as a simian homolog of HHV-7 was further confirmed by phylogenetic analysis, which showed a close relationship between the known human HHV-7 strains and the novel MneHV7. Additionally, MneHV7 clustered most closely with recently discovered HHV-7 homologs in great apes, including gorillas and a number of chimpanzee species ( 18 ). All HHV-7 homologs clustered clearly separately from both human HHV-6A and HHV-6B species and HHV-6 primate homologs, indicating the presence of two distinct roseolovirus lineages that we provisionally named roseolo 1 and roseolo 2.…”

“…Recently, Lavergne et al have reported the existence of HHV-7 simian homologs naturally infecting African great apes, including chimpanzees and gorillas ( 18 ). The study determined the complete sequence of the viral polymerase gene and a partial sequence of the glycoprotein B gene for each host species.…”

“…Recently, we and others have reported the existence of HHV-7 homologs naturally infecting different nonhuman primate species, including macaques ( 17 ) and great apes ( 18 ). All simian homologs of HHV-7 were discovered using consensus-degenerate hybrid oligonucleotide primers (CODEHOP) ( 19 ).…”

A glycan shield on chimpanzee CD4 protects against infection by primate lentiviruses (HIV/SIV)

“…Importantly, roseoloviruses closely related to HHV-7 have been identified in chimpanzees (57). Further investigation is warranted to determine whether chimpanzee-specific CD4 glycans influence entry of viruses other than HIV/SIVcpz.…”