MMTV-like Env sequences from human breast cancer patients cannot yet be considered as a separate species

Abstract

Background: Mouse mammary tumour virus (MMTV), a betaretrovirus, causes breast cancer in mice. Since its discovery, scores of studies have reported the detection of MMTV-like antigens and sequences primarily in human breast cancer, but not normal tissues. The presence of these sequences in humans has been hypothesised to be possibly due to zoonosis of MMTV into humans, named human mammary tumour virus (HMTV). However, many groups have not been able to repeat these findings, making these observations controversial. Over the years, an increasing number of HMTV env gene sequences from human breast cancer patients worldwide have been deposited in GenBank and other repositories. Aims and Objectives: The aim of this study was to use the current bioinformatic tools to analyse these highly homologous sequences to determine if any signature sequences could be associated specifically with HMTV. Materials and Methods: We first built an MMTV env gene consensus sequence (MMTV_CON) from the 41 MMTV sequences available in the database that was used to align the reported HMTV sequences (n = 333). Results: As expected, the MMTV envs showed 4-5% genetic variation within the mouse isolates. Alignment of MMTV_CON with those from HMTV revealed ten nucleotide variations that were like those observed within MMTV env, showing that the two viral strains could not be distinguished. Conclusion: Thus, we conclude that despite extensive data, inadequate env coverage, conservation of MMTV and HMTV envs and limitations in HMTV study design suggest that HMTV cannot be considered a separate species until the availability of more data covering full-length env or HMTV genome.