Research Summary

The central effort of our laboratory is a detailed analysis of the replication cycle of a retrovirus causing mammary carcinomas and T-cell lymphomas in mice, mouse mammary tumor virus (MMTV). 

We and others recently discovered a novel virus-encoded protein, Rem, which facilitates the nuclear export and expression of unspliced viral RNA containing a binding site for Rem. However, in contrast to another retrovirus, human immunodeficiency virus type 1 (HIV-1), which also encodes an RNA export protein (Rev), Rem is not required for nuclear export of env mRNA.

Therefore, our interest lie in determining the cellular factors involved in the post-transcriptional regulation of expression of env mRNA.

We are also studying the tropism of MMTV. Interestingly, we found that MMTV rapidly spreads in cultured human breast cells and that the virus spread is not blocked by an intrinsic

immunity factor, APOBEC3G, which restricts infection with HIV-1.

These results further substantiate the possibility that MMTV may be involved in some human diseases including human breast cancer.

Finally, we found that MMTV integrates randomly in the host chromosomes, which markedly contrasts with the integration preference of other retroviruses. We are currently in the process of generating an MMTV-based vector, which will be safer DNA delivery tool when compared to the commonly used vectors based on lentiviruses (HIV-1) and gammaretroviruses (murine leukemia virus, MLV), preferentially integrating within genes and transcription initiation sites, respectively.

 

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Stanislav Indik PhD.
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