The major homology region of bovine leukaemia virus p24gag is required for virus infectivity in vivo.

Abstract

In order to gain insight into the role of the major homology region (MHR) in the infectious potential of bovine leukaemia virus (BLV), mutations were introduced into the capsid gene of an infectious molecular clone. A provirus that was designed to contain only a slightly modified version of the MHR (substitution of phenylalanine 147 with a tyrosine) was still infectious in vivo. Furthermore, the provirus loads were not significantly different from those obtained with a wild-type virus. A second mutant was designed to analyse a mild modification of the MHR at the level of arginine 150. The substitution of this residue with a lysine completely destroyed the infectious potential of the recombinant virus. Finally, a third mutant that was deleted in the MHR region was unable to infect the host. Thus it appears that the integrity of the MHR domain is essential for BLV infectivity in vivo.

Discordance between Bovine Leukemia Virus Tax Immortalization In Vitro and Oncogenicity In Vivo

“…Sheep were infected with a wild-type strain (plasmid pBLV344 in animal 235), with viruses propagating with equivalent efficiencies and inducing pathogenesis after similar latency periods (plasmid pBLVIX in 8, 11, 247, 292, and 293 and pBLVgag150 in 175), or with the Tax mutant (pBLVTax106ϩ293 in 103, 104, 296, and 480). The construction of the pBLV344, pBLVIX, pBLVgag150, and pBLVTax106ϩ293 recombinant proviruses has been described elsewhere (73,75,77). Of note, the pBLVgag150 mutant, which was initially referred to as attenuated (75), appeared to induce pathogenesis at later times in sheep 175.…”

“…The construction of the pBLV344, pBLVIX, pBLVgag150, and pBLVTax106ϩ293 recombinant proviruses has been described elsewhere (73,75,77). Of note, the pBLVgag150 mutant, which was initially referred to as attenuated (75), appeared to induce pathogenesis at later times in sheep 175. Finally, three sheep (113, 114, and 115) were used as uninfected controls.…”

Viral DNA Synthesis Defects in Assembly-Competent Rous Sarcoma Virus CA Mutants

“…The result has been a perplexing array of phenotypes. In Ty3, human immunodeficiency virus type 1 (HIV-1), RSV, MuLV, Mason-Pfizer monkey virus (M-PMV), and bovine leukemia virus, many substitutions completely abolish particle assembly or cause the release of particles of aberrant morphology (1,12,31,36,40,44). Also, certain mutations that alter or delete the MHR sequence of HIV-1 Gag have been reported to cause defects in Gag-membrane binding (17) and in Gag-Pol packaging into particles (24,39).…”

“…Also, certain mutations that alter or delete the MHR sequence of HIV-1 Gag have been reported to cause defects in Gag-membrane binding (17) and in Gag-Pol packaging into particles (24,39). A number of additional MHR mutations have been described in RSV, MuLV, HIV-1, M-PMV, and bovine leukemia virus that have no discernible defect in assembly yet cause a severe loss of infectivity (1,12,31,40,44). Likewise, certain Ty3 mutations also result in the formation of particles that have severe defects in reverse transcription and transposition (36).…”

Molecular Characterization of Partial Sequences of Brazilian BLV Gag Sequences

“…The p24 protein has one of the most conserved regions of the gag gene, the major homology region (MHR) constituted by 20 aminoacids, which is present in the CA of most retroviruses and has an essential role in viral infectivity (Coffin et al 1997, Willems et al 1997. The p24 protein also contributes to gag polyprotein packing during viral assembly and it is important in the early stages of infection by interaction with cyclofilin A (Gamble et al 1996).…”