GENETIC STRUCTURE OF MURINE RETROVIRUSES

遗传变异是由点突变或重组引起的

Genetic variation as a result of point mutation or recombination occurs in all retrovirus infections including avian, murine and human retroviruses such as HIV. Such variation often has a profound influence on the infectious, replicative and pathogenic properties of the viruses. Mice inoculated with certain retroviruses generate variant retroviruses with altered infectious properties. The variants are the result of recombination of the inoculated virus with endogenous retroviral gene sequences of the mouse. The variants utilize a different cell surface receptor for infection, thus altering the infectious host range and have been implicated in a variety of proliferative diseases in the mouse. There exist 30 to 40 distinct retroviral sequences in the mouse genome which encode the receptor binding specificity exhibited by the variants, however which of these participate in recombination is unknown. Identification of the participants in the recombination process is essential to its understanding. It is clear from previous analyses of virion RNAs that the variants are not all derived from the same endogenous sequence. Furthermore, we have identified two different antigenic subgroups of the variants which correspond to two different subgroups of endogenous sequences and have found that different retroviruses preferentially recombine with different sets of endogenous sequences. Our most recent studies have been directed at: 1) the precise identification of the endogenous sequences which participate in recombination and: 2) the identification of viral genes of the inoculated viruses which influence recombination with particular sets of endogenous sequences. Sequence comparisons of the variant viruses with retroviral gene sequences from uninfected mice have identified particular endogenous genes which give rise to the recombinant viruses. Further analyses will reveal additional endogenous genes which participate in recombination and the frequency with which they do so. With regard to the viral gene(s) which influence the specificity of recombination, we have examined variants generated after infection of mice by chimeric viruses constructed between two retroviruses which clearly differ in the subgroups of variants generated. We have found that a region of the genome which encompasses the gene encoding the nucleocapsid protein of the virus strongly influences the recombinant subgroups identified in infected mice. Further studies may more precisely determine a smaller sequence responsible for this effect and may identify other regions of the genome which influence the specificity of recombination.