PMC

Structure and genome of a gammaretrovirus. The nucleocapsid is built from a hexameric lattice []. MA: matrix (p15), CA: capsid (p30), NC: nucleocapsid (p10), PR: protease, RT: reverse transcriptase (shown as a green dot), RH: RNAse H, IN: integrase, SU: surface unit (gp70), and TM: transmembrane protein (p15E). P12 is a small protein encoded from the portion between p15 and p30 in gag. LTR: long terminal repeat. The translation of glycoGag and normal Gag is indicated by the respective ribosome symbols. A Gag-Pol polyprotein is occasionally produced by suppression of a stop codon at the end of gag.

gag sequences of 300 high scoring mouse gammaretroviral sequences were aligned together with reference sequences. MLV sequences with ascribed tropism, from GenBank, were also added. The tree was rooted with a divergent rabbit gammaretrovirus-like sequence from scaffold 34, position 34101473 (oryCun1 assembly). Sequences in red (“HMRV”) are from the paper of Lo et al. []. They were from ME/CFS patients (“CFS”) or blood donors (“BD”). Two blood donor sequences from the Lo et al. study came out at the base of group G2, in other trees (not shown) at the base of group G3. The other emerged in group G3. The branch labels are either ERV host genus, chromosomal position, provisional genus (“C”: gamma), and ReTe score, or a reference Pol name. Genomic ERV sequences taken from the prototype of RetroBank were named as oryCun: rabbit, cavPor: guinea pig, felCat: cat, panTro: chimpanzee, or rheMac: rhesus macaque. Mouse sequences are just shown with their chromosomal location.

MLLVs have spread among vertebrates in recent evolutionary time. The approximate time estimates to the last common MLLV progenitor are based on references given in the text, and on the phylogenetic analysis of . Some gibbon apes in captivity have gibbon ape leukemia virus (GaLV). Koalas have recently been infected with koala retrovirus (KoRV). More distant relatives of the murine MLVs occur in pigs and cats. Porcine MLLV ERVs (PERVs) are MLLVs but the interspecies transmission routes are uncertain. Cats have several endogenous and exogenous MLLVs, including feline leukemia virus (FeLV). Birds have recently been infected with reticuloendotheliosis virus (REV). REV is not strictly an MLLV, but is a gammaretrovirus highly related to MLLVs. Its origin is uncertain, but its closest relatives are the ERV-T-like proviruses from opossum and primates. Humans may also recently have been infected with murine MLLVs, namely XMRV, although there are now indications that this is a laboratory contamination with the 22Rv1 virus. Endo-: endogenous retrovirus. Exo-: exogenous retrovirus.

Neighbor-joining (NJ) tree based on Pol amino acid sequences of 300 high ReTe scoring MLLVs, the same as in . The three high-scoring murine gamma groups (G1–G3) segregate in a similar way as in a gag nt-based tree (). Bootstrap values are shown to the left of each branch. Structurally intact proviruses are marked with green arrows. GLN virus [], MmERV, Mus dunni ERV (MdERV), AKV MLV, and XMRV (VP62 clone) are marked with magenta arrows. Murine MLLVs occur from the black arrow in the tree and upwards. The branch labels are either ERV host genus, chromosomal position, ReTe score, provisional genus, “po” for Pol, PBS, and number of stops and frame shifts (“z 0/0” means 0 stops and 0 shifts in pol), or a reference Pol name. PBS assignments are made by the 1.01 version of RetroTector. A more complete interpretation of PBS sequences of the G1-G3 groups is given in a forthcoming publication (Elfaitouri et al., accepted in Plos One). The major one zinc finger branch is indicated by the hand symbol. Nonmurine gammaretroviral ERV sequences were taken from the prototype of RetroBank. Further information on which assemblies were used can be found in [].

Simplified phylogeny of gammaretroviruses based on over 2000 gammaretrovirus-like sequences with one zinc finger in Gag, from selected vertebrate genomes (in a first version of RetroBank) and reference gammaretroviruses. Retroviral groups which occur in phylogenetically distant vertebrate hosts, indicating cross-species transmission events, are shown in red. The neighbor-joining tree was based on an alignment of 105 reference and consensus Pol amino acid sequences. Only the major branches are shown. As explained in the text, they were provisionally named after the cosegregating HERV group. The group of “MLV-like viruses,” MLLVs, at least 60% similar in Pol, is boxed in. The similarity is calculated from the inverted ratio of the BLASTP score of the sequence against itself to another sequence, or to a consensus Pol sequence. Some two-zinc finger sequences (ERV-HF, containing HERV-H and HERV-F) were included as a reference. Although the clustering included several genomes, the groups were named from the human sequence representative. MuERV: mouse endogenous retrovirus. MmERV is from Bromham et al. [], and MdERV is Mus dunni ERV from Wolgamot et al. []. GLN MuERV is from Ribet et al. []. Symbols: ∗ position of XMRV/HMRV, § recombinant MuERV Sp496-5Sb [] from Mus spretus, ¤ hortulanus endogenous murine virus, HEMV, from Mus spicilegus [], # MuRRS [], and MuERVC []. An ERV-S sequence [] was used to root the tree. It came from HERV-S, a sequence intermediate to spuma-, epsilon-, and gammaretroviruses. It belongs to the so-called “ERV3 family” according to the RepBase nomenclature []. This large clade is also called “Class III ERVs.” It should not be confused with the ERV3 group shown in the figure. The hand symbols denote proviruses with one and two zinc fingers in Gag, respectively. The murine gammaretroviral groups G1-G3 are described in greater detail in a forthcoming paper (Elfaitouri et al., accepted, Plos One).