Generation of AKR mink cell focus-forming viruses: a conserved single-copy xenotrope-like provirus provides recombinant long terminal repeat sequences

Abstract

AKV and AKR mink cell focus-forming virus-specific probes from the envelope and long terminal repeat (LTR) regions were prepared for study of the structure of recombinant proviruses in tumor tissues of AKR mice. The results showed that (i) all somatically acquired proviruses possessed, besides a recombinant gp7O gene, an altered U3 LTR; (ii) in a substantial portion of the somatically acquired AKR mink cell focusforming proviruses, the LTR comprised sequences derived from the same xenotropic-like provirus; (iii) this U3 LTR donating parental provirus (Xeno-dL) was present only once per genome equivalent in several mouse strains; (iv) in the strains containing the Xeno-dL provirus, the provirus was present in the same chromosomal site; (v) restriction analysis of the Xeno-dL revealed that the mink cell focus-forming gp7O sequences were derived from a parental provirus, different from Xeno-dL. Therefore, at least two nonecotropic parents participate in the generation of leukemogenic AKR mink cell focus-forming viruses: a xenotropic-like virus, Xeno-dL, donating U3 LTR sequences, and another xenotropic-like virus or viruses providing gp7O sequences.

T lymphomagenesis is determined by a dominant host gene thymic lymphoma susceptible mouse-1 (TLSM-1) in mouse models.

“…AKR endogenous ecotropic viruses, however, are only weakly lymphomagenie by themselves and the type of lymphoma seems not to be determined by virus alone, because Emv-ll or -12 congenie NIH-Swiss strain mice develop follicular center cell lymphomas (mature B lineage lymphoma) rather than T lymphomas (4). Thymotropic and leukemogenic virus in AKR is not encoded in germline: it is generated by successive recom-binational events among three endogenous parental viruses (5,6). First, an endogenous ecotropic virus, for example Emv-11, -12, or -14, acquires an env segment from a nonecotropic parent, and thus obtains a broader host range.…”

Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens.

“…A polyclonal goat anti-p30 serum (reactive with p30 and its precursor polyproteins) was used in addition to a panel of mAbs reactive with env proteins: anti-gp70f mAb 35/56, and anti-p15E" mAb 19-F8 react with a highly conserved gp70 and p15E epitope, respectively. These epitopes are expressed by both MCF and ecotropic virions and on the cell surface ofMCF and ecotropic virus-infected Location of MuLV specific hybridization probes (derived from references [41][42][43][44] . The positions of some restriction sites are indicated (in kb): K, Kpnl, B, Barn HI; Sm, Sma I, R, Eco RI, Sa, Sau 3a ; P, Pst 1.…”

“…Donor (d) and acceptor (a) splice sites are indicated with arrows . Virusspecificity: +, probe hybridizes to (MCF or ecotropic) sequences of the majority of exogenous MuLV; -, probe does not hybridize to (MCF or ecotropic) sequences of the majority of exogenous MuLV (41)(42)(43)(44).…”

“…Probes were nick translated with 12 P-dCTP to specific activities of 7-8 x 108 cpm/Feg . The isolation and characterization ofthe MuLVspecific hybridization probes have been described (41)(42)(43). Probes corresponding to the middle and COOH-terminal region ofp15E ofecotropic AKV MuLV (MCp15E probe), the U3LTR of ecotropic AKV MuLV (AKVLTR probe), the NH2-terminal part of the gp70 region of ecotropic AKVMuLV (eco gp70 probe), and the NH2-terminal part of the gp70 region of MCF-MuLV (MCF gp70 probe) were used.…”

Reflections on scrapie and related disorders, with consideration of the possibility of a viral aetiology

“…MCF-like viruses have also been recovered from feline (Neil et aL, 1991) and avian oncogene-murine chimeric systems (Feuer et aL,i993). Other references that provide a useful entry to this field include Adachi et al (1984), Chattopadhyay et aL (1991), Di Fronzo and Holland (1993), Khan et aL (1987), Koch et aL (1984), Levy et al (1985), Makino et al (1990), Oliff et al (1984), Quint et al (1984) and Shields et al (1991).…”