An increase in disease latency is associated with a host-dependent selection for recombinant murine leukemia viruses with substitutions in the p15E (TM) gene.
The genomes of recombinant murine leukemia viruses recovered from HRS/J (type I env recombinants) and CWD (type II env recombinants) mice have distinct envelope gene structures. To better understand the biologic significance of these differences, we examined the differences in the responses of HRS/J and CWD mice to inoculation with an oncogenic type II env recombinant. The CWD recombinant accelerated the onset of lymphoma in both strains, but the disease latency in the HRS/J mice was about 2 months longer. Analysis of the recombinant viruses in the HRS/J tumors revealed that the injected type II env recombinant had recombined in vivo with the endogenous ecotropic viruses to generate secondary recombinants with type I envelope genes. In another set of experiments, comparison of complete or partial DNA sequences of the envelope genes from six recombinant proviruses confirmed that the origins of the sequences that encode an amino-terminal region of the TM envelope protein, p15E, distinguish type I envelope genes from type II. Taken together with the results of previous studies, these observations suggest that the differences in the responses of HRS/J and CWD mice to the oncogenic type II env recombinant resulted from an interaction between the viral TM protein and a host factor expressed in HRS/J mice.
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
C Y
CY
Thomas
M A
MA
Coppola
J D
JD
Nuckols
S C
SC
Lawrenz-Smith
A C
AC
Massey
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004274:DNA, Recombinant / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007942:Leukemia, Experimental / Q000209:etiology; D008223:Lymphoma / Q000209:etiology; D051379:Mice; D008812:Mice, Hairless / Q000382:microbiology; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000235:genetics*
D004274:DNA, Recombinant; D004279:DNA, Viral; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C078678:p15E protein, Murine leukemia virus