Novel Virus Related to Kaposi’s Sarcoma–Associated Herpesvirus from Colobus Monkey

Abstract

We determined the complete genome sequence of a virus isolated from a mantled guereza that died of primary effusion lymphoma. The virus is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV) but lacks some genes implicated in KSHV pathogenesis. This finding may help determine how KSHV causes primary effusion lymphoma in humans. K aposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma, primary effusion lymphoma, and the plasma cell variant of multicentric Castleman disease in humans (1). KSHV-related viruses (also known as rhadinoviruses) naturally infect New and Old World primates (2-5). Old World primate rhadinoviruses fall into 2 lineages, rhadinovirus 1 (RV1) and rhadinovirus 2 (RV2) (2,6). The RV1 lineage contains KSHV; the retroperitoneal fibromatosis-associated herpesviruses (RFHVs) identified in Macaca nemestrina, M. fascicularis, and M. mulatta macaques; and closely related viruses of other Old World primates (2,5). The RV2 lineage contains macaque viruses more distantly related to KSHV, such as rhesus macaque rhadinovirus, M. nemestrina RV2, M. fascicularis RV2, and Japanese macaque rhadinovirus (2,7). Complete genome sequences of the RV1 lineage viruses KSHV and RFHV of M. nemestrina macaques (RFHVMn), as well as

Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases

“…A phylogenetic tree based on the amino acid sequences of available gamma-herpesvirus RNRs indicates that the sequences from human, rhesus macaque, and marmoset Lymphocryptoviruses cluster together and the sequences from the different Rhadinoviruses cluster according to viral lineage ( Figure 8E ). Interestingly, despite its similarity to KSHV ORF61, the RNR from ColHV-1—a novel KSHV-related virus identified in African Colobinae monkeys ( Dhingra et al, 2019 )—differs from the RNRs of all other viruses that infect Catarrhini primates tested here in that it shows no ability to bind, relocalize, or inhibit present-day human or ancestral A3B ( Figure 8B , Figure 8—figure supplement 2A , and Figure 8D ) or interact with its host’s A3A ( Figure 8—figure supplement 3A ). This apparent incongruity may be explained by the fact that African Colobinae monkeys appear to have lost the A3B gene following the Colobinae subfamily split into the African and Asian tribes 10–14 million years ago ( Figure 8—figure supplement 3B–C ), which presumably relieved the pressure for ColHV-1 to maintain an A3B-neutralization activity.…”

Evidence linking APOBEC3B genesis and evolution of innate immune antagonism by gamma-herpesvirus ribonucleotide reductases

“…A phylogenetic tree based on the amino acid sequences of available gamma-herpesvirus RNRs indicates that the sequences from human, rhesus macaque, and marmoset Lymphocryptoviruses cluster together and the sequences from the different Rhadinoviruses cluster according to viral lineage ( Figure 8E ). Interestingly, despite its similarity to KSHV ORF61, the RNR from ColHV-1—a novel KSHV-related virus identified in African Colobinae monkeys [45]—differs from the RNRs of all other viruses that infect Catarrhini primates tested here in that is shows no ability to bind, relocalize, or inhibit present-day human or ancestral A3B ( Figure 8B , Figure 8—figure supplement 2A , and Figure 8D ) or interact with its host’s A3A ( Figure 8—figure supplement 3A ). This apparent incongruity may be explained by the fact that African Colobinae monkeys appear to have lost the A3B gene following the Colobinae subfamily split into the African and Asian tribes 10 to 14 million years ago ( Figure 8—figure supplement 3B-C ), which presumably relieved the pressure for ColHV-1 to maintain an A3B-neutralization activity.…”

“…Lymphocryptoviruses cluster together and the sequences from the different Rhadinoviruses cluster according to viral lineage (Figure 8E). Interestingly, despite its similarity to KSHV ORF61, the RNR from ColHV-1-a novel KSHV-related virus identified in African Colobinae monkeys [45]-differs from the RNRs of all other viruses that infect Catarrhini primates tested here in that is shows no ability to bind, relocalize, or inhibit present-day human or ancestral A3B (Figure 8B, Differential binding of viral RNRs to present day and ancestral A3B is likely a reflection of past-and possibly still ongoing-genetic conflicts. To further explore this idea, we analyzed a data set of primate A3B DNA sequences for evidence of codon sites under diversifying/positive selection using the mixed effects model of evolution algorithm (MEME) [46].…”