A large number of the human microRNAs target lentiviruses, retroviruses, and endogenous retroviruses

Hakim, Shazia Tabassum; Alsayari, Mohammad; McLean, David C.; Saleem, Sajid; Addanki, Krishna C.; Aggarwal, Mayank; Mahalingam, Kuha; Bagasra, Omar

doi:10.1016/j.bbrc.2008.02.025

Cited by 42 publications

(35 citation statements)

References 33 publications

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“…Viral RNA is also a target for antiviral responses that result in specific transcript degradation and low protein expression. Recently, a large number of microRNAs that target exogenous and endogenous retroviruses, including HERV-K, have been identified (28). The roles played by such silencing small RNAs in the inefficient expression of HERV-K proteins deserve further investigation.…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of the Ancestral Glycoprotein of Human Endogenous Retrovirus K and Modulation of Its Functional Activity by Truncation of the Cytoplasmic Domain

Hanke

Krämer

Seeher

et al. 2009

J Virol

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Endogenous retroviruses present in the human genome provide a rich record of ancient infections. All presently recognized elements, including the youngest and most intact proviruses of the human endogenous retrovirus K(HML-2) [HERV-K(HML-2)] family, have suffered postinsertional mutations during their time of chromosomal residence, and genes encoding the envelope glycoprotein (Env) have not been spared these mutations. In this study, we have, for the first time, reconstituted an authentic Env of a HERV-K(HML-2) provirus by back mutation of putative postinsertional amino acid changes of the protein encoded by HERV-K113. Aided by codon-optimized expression, we demonstrate that the reconstituted Env regained its ability to be incorporated into retroviral particles and to mediate entry. The original ancient HERV-K113 Env was synthesized as a moderately glycosylated gp95 precursor protein cleaved into surface and transmembrane (TM) subunits. Of the nine N-linked oligosaccharides, four are part of the TM subunit, contributing 15 kDa to its apparent molecular mass of 41 kDa. The carbohydrates, as well as the cytoplasmic tail, are critical for efficient intracellular trafficking, processing, stability, and particle incorporation. Whereas deletions of the carboxy-terminal 6 residues completely abrogated cleavage and virion association, more extensive truncations slightly enhanced incorporation but dramatically increased the ability to mediate entry of pseudotyped lentiviruses. Although the first HERV-K(HML-2) elements infected human ancestors about 30 million years ago, our findings indicate that their glycoproteins are in most respects remarkably similar to those of classical contemporary retroviruses and can still mediate efficient entry into mammalian cells.

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Section: Discussionmentioning

confidence: 99%

Reconstitution of the Ancestral Glycoprotein of Human Endogenous Retrovirus K and Modulation of Its Functional Activity by Truncation of the Cytoplasmic Domain

Hanke

Krämer

Seeher

et al. 2009

J Virol

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“…The possibility that cellular microRNAs affect HTLV-1 expression has been addressed computationally in a study that compared the sequences of 451 human microRNAs with the genomes of a panel of endogenous and exogenous retroviruses that included HTLV-1 (Hakim et al, 2008). In the case of HTLV-1, this analysis yielded 7 microRNAs with greater than 80% sequence homology to the plus-strand.…”

Section: Do Cellular Micrornas Target Htlv-1 Transcripts?mentioning

confidence: 99%

Role of microRNAs in HTLV-1 infection and transformation

Ruggero

Corradin

Zanovello

et al. 2010

Molecular Aspects of Medicine

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“…There are numerous endogenous and exogenous passenger retroviruses in some of the human tumors that are targeted for viral therapy (teratocarcinomas, melanoma, certain adenocarcinomas of breast, ovary, and prostate, certain sarcomas) (reviewed in [360]). Endogenous retroviruses are activated by stress signals [56] and by the impediment of innate and adaptive immune faculties in immunosuppressed individuals [470]; however, the ancient microRNA/small inhibitory RNA defense reactions remain active [142]. Oncolytic viral therapy is being extended for the treatment of these tumors.…”

Section: The Resident Viral Flora (Endogenous Retroviruses Potentialmentioning

confidence: 99%

Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers

Sinkovics

Horváth

2008

Arch. Immunol. Ther. Exp.

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Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a combination of naturally oncolytic viruses and wild-type viruses rendered oncolytic and harmless by genetic engineering, that will induce complete remissions of human tumors. It may be necessary to co-administer certain chemotherapeutic agents, advanced cancer vaccines, or even immune lymphocytes, and targeted therapeuticals, to ascertain, that remissions induced by the viral agents will remain complete and durable; will co-operate with anti-tumor host immune reactions, and eventually will result in cures of advanced metastatic human cancers.

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A large number of the human microRNAs target lentiviruses, retroviruses, and endogenous retroviruses

Cited by 42 publications

References 33 publications

Reconstitution of the Ancestral Glycoprotein of Human Endogenous Retrovirus K and Modulation of Its Functional Activity by Truncation of the Cytoplasmic Domain

Reconstitution of the Ancestral Glycoprotein of Human Endogenous Retrovirus K and Modulation of Its Functional Activity by Truncation of the Cytoplasmic Domain

Role of microRNAs in HTLV-1 infection and transformation

Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers

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