Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)

Abstract

Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV-and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of Melomys burtoni from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in M. burtoni provides further evidence that M. burtoni, and potentially other lineages within the widespread subfamily Murinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of M. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents. IMPORTANCEGibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate host whose range overlaps those of both gibbons and koalas. Using hybridization capture and high-throughput sequencing, we have screened a wide range of rodent candidate hosts from Southeast Asia for KoRV-and GALV-like sequences. Only a Melomys burtoni subspecies from Wallacea (Indonesia) was positive for GALV. We report the genome sequence of this newly identified GALV, the critical domain for infection of its potential cellular receptor, and its phylogenetic relationships with the other previously characterized GALVs. We hypothesize that Melomys burtoni, and potentially related lineages with an Australo-Papuan distribution, may have played a key role in crossspecies transmission to other taxa. The evolutionary mechanisms involved in cross-species transmissions (CSTs) of viruses are complex and generally poorly understood. Viral evolution, host contact rates, biological similarity in host defense systems (receptors, viral restriction factors), and host evolutionary relationships have been proposed as key factors in CST rates and outcomes (1). However, the...

Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV)

“…Recently, a new gammaretrovirus, Melomys woolly monkey virus (MelWMV), was detected in another Melomys burtoni subspecies living in the Wallacea in Indonesia [13]. This virus was detected as a result of screening 26 Southeast Asian rodent species and all other 25 species were negative.…”

“…MelWMV has 98% homology with the WMV and is a subtype of WMV, whereas MbRV from the Australian animals is a sister taxon (Figure 1a). Stop codons in env and pol indicate that it is a defective, endogenous retrovirus [13]. Since MelWMV und MbRV are the closest relatives to GaLV, they could be the origin of GaLV, although it is also possible that the two Melomys subspecies were infected by a GaLV-like virus from an unknown species.…”

“…Secondly, why is WMV more closely related to MbRV than to GaLV, even though WMV is the result of an infection of a woolly monkey with GaLV, whereas MbRV is suggested to be the precursor of the GaLV? Thirdly, the GaLV/KoRV-like viruses found until now in the Melomys subspecies [12,13] and in bats [14] have been integrated into the genome of these species a long time ago and they are now defective. Based on the similarity of its 5′ and 3′ long terminal repeats (LTR), MelWMV integrated into the genome of the Indonesian melomys 200,000 years ago [13].…”

“…Many birds do not cross the Wallace line, but some animals do, such as bats and crab-eating macaques [7,8]. Searching for the precursor virus, retroviruses related to KoRV and GaLV have been described in rodents such as South East Asian mice (e.g., Mus caroli [9,10] and Mus dunni [11]), as well as in two subspecies of Melomys burtoni in Australia and Indonesia [12,13]. Although these viruses are close relatives, it is still difficult to explain how gibbons and koalas, living in such diverse habitats, could be infected with the precursor virus.…”

Phylogenetic Diversity of Koala Retrovirus within a Wild Koala Population

“…The 108 env sequences obtained here were combined with nine previously reported unique KoRV env sequences, seven retrieved from GenBank (accession numbers AF151794, KP792564, KP792565, KC779547, AB822553, AB828004, and AB828005) and two unique sequences supplied by Maribeth Eiden (21). In addition, four sequences were utilized as outgroups to root the KoRV phylogeny: two of GALV (GenBank accession numbers KT24047 and KT24048) and two of WMV (KT724051 and KX059700, with the latter sampled from a rodent, Melomys burtoni [31]). These sequences were then aligned using MUSCLE (32) with default parameters ensuring that the nucleotide sequence alignment properly matched triplet codon structure.…”