DNA sequence of mutations induced in cells by herpes simplex virus type-1

Hwang, Charles B. C.; Shillitoe, Edward J.

doi:10.1016/0042-6822(90)90392-5

Cited by 27 publications

(13 citation statements)

References 46 publications

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“…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). It has been hypothesized (12,26) that herpesvirus DNAs might cause mutations by movement of insertion sequence-like elements present in the viral genomes.…”

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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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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“…110 A number of tumor viruses are known to interfere with other DNA repair pathways and induce mutagenesis. 17,[111][112][113] In addition, the human immunodeficiency virus (HIV) Vpr protein induces the degradation of UNG and SMUG, implying that HIV infected cells may also be deficient in BER. 114 It is not know whether this activity plays a role in the increased incidence of cancer in AIDS patients.…”

Section: Linkage Between Aberrant Ber and Cancermentioning

confidence: 99%

Is Base Excision Repair a Tumor Suppressor Mechanism?

Sweasy¹,

Lang²,

DiMaio³

2006

Cell Cycle

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The base excision repair pathway is critical for the removal of oxidized and methylated bases from the DNA. Much of this DNA damage arises endogenously, as a result of oxygen metabolism. Several proteins including DNA glycosylases, the APE1 endonuclease, DNA polymerase β and DNA ligase, act in a highly regulated and coordinated manner during base excision repair to excise the base adducts from the DNA and restore the normal DNA sequence. Both germline and tumor-associated variants of genes encoding these proteins have been identified in humans. In many cases, the protein variant has been shown to have properties that could contribute to the development of cancer, suggesting that base excision repair acts as a tumor suppressor mechanism in humans. Limited epidemiological studies are consistent with this view. Our review of the literature indicates that additional laboratory and epidemiological studies of the role of base excision repair in cancer etiology is warranted.

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“…This results in some but not all of the features of malignancy [165]. Neither the mutations nor the phenotypic changes are sufficiently specific to act as markers by which a herpes-induced malignancy could be diagnosed [166]. Recent years have seen little or no progress in the study of HSV and its malignant potential.…”

Section: Herpes Simplex Virus (Hsv)mentioning

confidence: 99%

Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

Gupta

Metgud

2013

Pathology Research International

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Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined.

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DNA sequence of mutations induced in cells by herpes simplex virus type-1

Cited by 27 publications

References 46 publications

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

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

Is Base Excision Repair a Tumor Suppressor Mechanism?

Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

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