Influence of Long Terminal Repeat and Env on the Virulence Phenotype of Equine Infectious Anemia Virus

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FONTE

American Society for Microbiology

RESUMO

The molecular clones pSPeiav19 and p19/wenv17 of equine infectious anemia virus (EIAV) differ in env and long terminal repeats (LTRs) and produce viruses (EIAV19 and EIAV17, respectively) of dramatically different virulence phenotypes. These constructs were used to generate a series of chimeric clones to test the individual contributions of LTR, surface (SU), and transmembrane (TM)/Rev regions to the disease potential of the highly virulent EIAV17. The LTRs of EIAV19 and EIAV17 differ by 16 nucleotides in the transcriptional enhancer region. The two viruses differ by 30 amino acids in SU, by 17 amino acids in TM, and by 8 amino acids in Rev. Results from in vivo infections with chimeric clones indicate that both LTR and env of EIAV17 are required for the development of severe acute disease. In the context of the EIAV17 LTR, SU appears to have a greater impact on virulence than does TM. EIAV17SU, containing only the TM/Rev region from the avirulent parent, induced acute disease in two animals, while a similar infectious dose of EIAV17TM (which derives SU from the avirulent parent) did not. Neither EIAV17SU nor EIAV17TM produced lethal disease when administered at infectious doses that were 6- to 30-fold higher than a lethal dose of the parental EIAV17. All chimeric clones replicated in primary equine monocyte-derived macrophages, and there was no apparent correlation between macrophage tropism and virulence phenotype.

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