Functional analysis of human cytomegalovirus morphological transforming region II (mtrll)

Razzaque, Abdur; Zhu, F.; Jones, Clinton

doi:10.1016/0042-6822(91)90513-b

Cited by 17 publications

(10 citation statements)

References 11 publications

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“…A viral transforming gene, called MtrII, is located within the region of map units 0.685-0.770 in HCMV genome. The expression of MtrII results in transformation of NIH 3T3 cells (Choudhury et al, 1992;Doniger et al, 1999;Jahan et al, 1989;Muralidhar et al, 1996;Razzaque et al, 1988;Razzaque et al, 1991;Thompson et al, 1994;Wang and Razzaque, 1993). Sequence analysis revealed that the MtrII gene is in fact the first exon of vIL-10A.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169

et al. 2008

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Two products of human cytomegalovirus (HCMV) UL111a gene have been previously identified to resemble human IL-10 (hIL-10). These viral IL-10s (vIL-10s) are able to induce signal transduction events and biological activities in a variety of cells. In this study, five novel vIL-10 transcripts were identified from HCMV AD169 infected MRC-5 cells. Some vIL-10 isoforms were posttranslationally glycosylated, depending on the existence of a predicted N-linked glycosylation site. Similar to hIL-10, four of the vIL-10 isoforms apparently formed putative dimers. Among the different vIL-10 isoforms, vIL-10A significantly induced the phosphorylation of transcription factor STAT3 in THP-1 cells. All identified vIL-10 isoforms were able to form complexes with hIL-10, and enhanced hIL-10-induced STAT3 phosphorylation in different degrees. Identification of diverse forms of vIL-10 suggests that HCMV has developed a sophisticated mechanism to interfere with hIL-10 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169

et al. 2008

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“…Earlier reports have documented the transforming potential of both herpes simplex virus and HCMV DNAs and have demonstrated that viral DNA is often not retained in transformed cells and tumor samples (4,12,26,27,(34)(35)(36)(37)(38). Further, several studies have indicated that infection with herpesviruses or transfection with viral DNA induces mutations in cellular genes (12,(39)(40)(41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus IE1 and IE2 proteins are mutagenic and mediate “hit-and-run” oncogenic transformation in cooperation with the adenovirus E1A proteins

Shen

Zhu²,

Shenk

1997

Proc. Natl. Acad. Sci. U.S.A.

164

109

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Some epidemiological studies have suggested a possible link between human cytomegalovirus (HCMV) infection and various malignancies, and HCMV has been shown to transform cultured cells. However, viral DNA is not detected in most transformants, and the mechanism by which HCMV might contribute to oncogenesis has remained obscure. Here we show that the HCMV immediate early 1 and 2 genes can cooperate with the adenovirus E1A gene to generate transformed foci of primary baby rat kidney cells. HCMV gene expression is transient and viral DNA is not present in clonal cell lines derived from the transformed foci. We find that the HCMV immediate early proteins are mutagenic, and we propose that HCMV has the potential to contribute to oncogenesis through a ''hit-and-run'' mechanism, by inducing mutations in cellular genes.Serological and molecular studies have suggested a possible association of human cytomegalovirus (HCMV) with the development of human malignancies, including cervical carcinoma, colon carcinoma, and prostate cancer (reviewed in refs. 1-5). A variety of laboratory observations demonstrate that HCMV has oncogenic potential, supporting the idea that HCMV might contribute to the induction of human tumors. HCMV has been shown to induce cervical neoplasia in mice (6), it can morphologically transform human (7,8) as well as other mammalian (9 -11) cells in culture, and HCMVtransformed cells can form tumors in experimental animals (6,8). In vitro assays have identified three regions on the HCMV genome with transforming activity (reviewed in ref. 5). However, if HCMV infection does contribute to tumor induction in humans, the mechanism underlying HCMV-induced oncogenesis is very likely different from that of DNA viruses that are known to play a role in human malignancies. Whereas specific viral genes are present and expressed in tumors induced by agents such as Epstein-Barr virus and the human papillomaviruses, no specific HCMV DNA sequence element is reliably present and often no viral DNA can be detected in cells transformed by HCMV (reviewed in refs. 4 and 12).We have previously reported (13) that the two most abundantly expressed immediate-early gene products of HCMV, IE1 and IE2 (reviewed in ref. 14), inhibit the induction of apoptosis by tumor necrosis factor ␣ (TNF-␣) or the adenovirus E1A oncoproteins. The fact that the IE1 and IE2 gene products are able to inhibit apoptosis raised the interesting possibility that they might cooperate with the adenovirus E1A oncoproteins to transform primary rodent cells, as do the adenovirus E1B 19-kDa (E1B) protein and the cellular Bcl-2 protein, each of which can block apoptosis (15,16). In this report, we show that the IE1 and IE2 gene products can, indeed, cooperate with E1A to transform primary baby rat kidney (BRK) cells. Unexpectedly, however, we find that expression of the IE1 and IE2 proteins is transient; HCMV proteins and DNA are not present in transformed cell lines derived from the foci. The IE1 and IE2 gene products are mutagenic, and we propose that...

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“…The DNA from nontransformed parental cells (WI-38) did not demonstrate detectable hybridization to the 32P-mPlI probe. These results correlate with analysis of DNA extracted from rodent cells transformed in vitro by CMV [10, 12,26] or with the finding from various human biopsies, in which a frequent occurrence of CMV-mMI-related sequences was demonstrated [5,13], The DNA blots were stripped and rehybridized with 32P-labeled mtrlll sequences. There was no detectable hybridization to the DNA from the CMV-transformed cell lines or from the parental cells (data not shown).…”

Section: Retention O F CMV Dna-related Sequences In Transformed Cellsmentioning

confidence: 62%

Alteration in the Coding Potential and Expression of H-ras in Human Cytomegalovirus-Transformed Cells

et al. 1994

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CMV-transformed cell lines demonstrated a greater level of H-ras RNA (7.5-to 9.5-fold) relative to the level for H-ras in parental cells. Nuclear run off assays showed that the RNA levels for the H-ras gene were regulated at the level of transcriptional initiation. The increased RNA levels for H-ras correlated with the level of p21^rasVal-12 in transformed cells, while p21^raíVal-12 was below the level of detection in nontransformed cells using Western blot analysis. In addition, an activating mutation was identified in both alleles of the first exon, codon 12 of H-ras resulting in a G:C to T:A transversion in all transformed cell lines examined in this study. These results suggest that the mutated H-ras may be one of the components by which an oncogenic phenotype is maintained in these CMV-transformed cells.

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Functional analysis of human cytomegalovirus morphological transforming region II (mtrll)

Cited by 17 publications

References 11 publications

Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169

Identification of novel viral interleukin-10 isoforms of human cytomegalovirus AD169

Human cytomegalovirus IE1 and IE2 proteins are mutagenic and mediate “hit-and-run” oncogenic transformation in cooperation with the adenovirus E1A proteins

Alteration in the Coding Potential and Expression of H-ras in Human Cytomegalovirus-Transformed Cells

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