A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome.

Herpes simplex virus (HSV) induces DNA amplification of target genes within the host cell chromosome. To characterize the HSV genes that mediate the amplification effect, combinations of cloned DNA fragments covering the entire HSV genome were transiently transfected into simian virus 40 (SV40)-transformed hamster cells. This led to amplification of the integrated SV40 DNA sequences to a degree comparable to that observed after transfection of intact virion DNA.

Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers.

Infections with specific types of human papillomaviruses (HPV) have emerged as necessary but not sufficient factors for the development, at least, of the majority of cervical, vulvar, penile, and perianal cancers. Evidence has accumulated for their causal role in the induction of anogenital premalignant lesions. Genetic events underlying the mechanism of anogenital carcinogenesis have become increasingly understood.

Two newly identified human papillomavirus types (HPV 40 and 57) isolated from mucosal lesions.

Two new papillomaviruses, HPV 40 and HPV 57, were isolated from a PIN lesion and an inverted papilloma of the maxillary sinus, respectively. HPV 40 showed a 13% homology to HPV 7 by reassociation kinetics and HPV 57 showed a 17% homology to HPV 2 and 25% homology to HPV 27. Hybridization of the DNA of these papillomaviruses to a wide variety of different tumor biopsies revealed that HPV 40 was present in a few genital condylomata acuminata as well as in bowenoid lesions.

Transformation of human cells by oncogenic viruses supports permissiveness for parvovirus H-1 propagation.

Parvovirus H-1 has been shown to suppress spontaneous and chemically or virally induced tumorigenesis in hamsters. In human cell culture systems propagation of H-1 is restricted to transformed cells, which are killed by H-1 infection, in contrast to normal diploid cells, which are nonpermissive for H-1. By analyzing the permissiveness of a variety of human cells for H-1, it was determined that the majority of tested transformed or immortalized cells which were permissive for H-1 contained the DNA of oncogenic viruses (human papillomavirus, simian virus 40, adenovirus, hepatitis B virus, Epstein-Barr virus, and human T-cell lymphotropic virus type I).

Host cell regulation of HPV transforming gene expression.

Infections with specific types of human pathogenic papillomaviruses, most notably HPV 16 and 18, appear to be necessary but not sufficient factors in the etiology of anogenital cancer. Recently their role in the induction of genital intraepithelial neoplasias became evident. The expression of specific HPV genes (E6-E7) emerges as an important prerequisite for the proliferative phenotype of cervical carcinoma cells.

Chromatin structure and transcriptional regulation of human papillomavirus type 18 DNA in HeLa cells.

Mapping analysis of the nucleosomal organization of integrated human papillomavirus type 18 (HPV18) DNA in HeLa cells reveals a very prominent nuclease-hypersensitive site within the viral noncoding regulatory region that harbors transcriptional control sequences and coincides with most of the 5' ends of the cytoplasmic early mRNAs. Moreover, it is shown that the conserved coamplified 5' cellular flank, common to all HPV18 copies in HeLa cells and located close to the virus-cell integration site, also contains several distinct hypersensitive sites, accessible not only to DNase I but also to restriction enzymes. Nuclear run-on analysis in isolated HeLa nuclei demonstrates the occurrence of nascent transcripts covering the cellular flank (the late and the viral noncoding regulatory region), indicating that a cellular promoter, marked by the hypersensitive sites, cooperates with the viral control region in generating the HPV18 transcripts.

Unusual HPV types in oral warts in association with HIV infection.

Human papillomaviruses (HPV) are associated with certain oral soft tissue lesions, such as papillomas, warts, condylomata, and focal epithelial hyperplasia (FEH). HPV types 2, 6, 11, 16, and 18 have been identified in some of these oral lesions, while HPV 13 and 32 are associated with FEH. Little is known about the HPV types in oral warts of persons infected with human immunodeficiency virus (HIV).

Human papillomavirus in dysplasia and carcinoma of the cervix in Singapore.

A prospective study was conducted in Singapore in 1985 where 107 women with abnormal cervical smears were studied for cervical neoplasia and its association with the human papillomaviruses (HPV), using HPV 11, 16 and 18 DNA as probes. Cervical biopsies were performed for histology as well as for DNA Southern Blot hybridization studies to detect the presence of HPV 11, 16 or 18 genome. The prevalence of the various types of papillomavirus DNA in cervical tissue samples from cervical carcinoma and dysplasias is presented.

Dissociation of carcinogen-induced SV40 DNA-amplification and amplification of AAV DNA in a Chinese hamster cell line.

Time kinetics of AAV-5 DNA amplification induced by MNNG in cells of a Chinese hamster line (CO631) and a Syrian hamster line (Elona) were compared to kinetics of SV40 DNA amplification in these cells. AAV-5 DNA amplification starts in both lines about 8 hr following treatment of AAV-infected cells with MNNG. SV40 DNA amplification is induced only in CO631 cells.

DNA amplification of adeno-associated virus as a response to cellular genotoxic stress.

We studied DNA amplification of helper virus-dependent parvoviruses [adeno-associated virus (AAV)] following genotoxic treatment of a number of mammalian cell lines from different species including primary, immortalized, and tumorigenic cells. All cell lines, either infected with AAV or transfected with parvoviral DNA, readily amplified AAV DNA in the absence of helper virus following treatment of cells with a wide variety of genotoxic agents like chemical carcinogens, UV, heat shock, and metabolic inhibitors of DNA replication or protein synthesis. In addition, we show that in the SV40-transformed Chinese hamster cell lines CO60 and CO631 carcinogen-induced AAV DNA amplification may result in a complete AAV replication cycle giving rise to infectious AAV progeny.

Adeno-associated viruses inhibit SV40 DNA amplification and replication of herpes simplex virus in SV40-transformed hamster cells.

Coinfection with HSV-1 and any of the three defective parvoviruses AAV-2, AAV-3, or AAV-5 reduces the HSV-1-induced amplification of SV40 DNA in the SV40-transformed hamster cell lines CO631 and Elona. Moreover, all three viruses significantly decrease HSV-1 replication. The effects are measurable to the same extent in both cell lines and are dependent on the quantity of AAV DNA molecules rather than on infectious AAV particles.

Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-azacytidine.

The transcription of human papillomavirus type 18 (HPV 18) is selectively suppressed in non-tumorigenic HeLa x fibroblast or HeLa x keratinocyte cell hybrids by 5-azacytidine. In contrast, viral gene expression is not influenced by 5-azacytidine in both tumorigenic hybrid segregants and in the parental HeLa cells. The suppression mechanism seems to operate at the level of initiation of transcription since nuclear run-on experiments show the absence of elongated nascent viral RNA, whereas the transcription of cellular reference genes remains unaffected.

Frequency of initial caries lesions as predictor of future caries increment in children.

The aim of this study was to evaluate the predictive power of the frequency of initial caries lesions in selecting persons at high risk for caries. The subjects (n = 124) were 11-13 yr old at the beginning of the follow-up. Caries was registered initially and and after 5 yr.

Characterization of a new human papillomavirus (HPV 41) from disseminated warts and detection of its DNA in some skin carcinomas.

A new human papillomavirus type (HPV 41), distantly related to known HPV prototypes, was isolated from a patient with disseminated facial, peri-anal and foot warts (epidermodysplasia verruciformis was not diagnosed). The viral DNA was molecularly cloned in 2 BamH1 restriction fragments with sizes of 6.5 kb and 0.

Streptococcus mutans counts obtained by a dip-slide method in relation to caries frequency, sucrose intake and flow rate of saliva.

The level of Streptococcus mutans in saliva was determined by a dip-slide method in 841 13-year-old children in order to identify children with high caries risk. For each child, the flow rate of saliva was determined. Caries scores were obtained from Public Dental Health records.

Human papillomavirus infections in women with and without abnormal cervical cytology.

9295 smears, obtained from women attending three gynaecological hospitals for routine screening, were examined for human papillomavirus (HPV) types 6 and 11 and HPV 16 and 18 infections by filter in-situ hybridisation. The data were compared with cytological findings. In women with normal cytological smears HPV infection was identified in about 10% of women aged between 15 and 50 years and in less than 5% of those aged over 50.

An amplification unit in human melanoma cells showing partial homology with sequences of human papillomavirus type 9 and with nuclear antigen 1 of the Epstein-Barr virus.

By partial homology with the DNA of human papillomavirus type 9 a cellular amplification unit was detected which is amplified in melanoma cells but not in Epstein-Barr virus-transformed B cells of two melanoma patients. A 2.4-kilobase EcoRI fragment of this amplification unit was cloned and designated mel/HPV9.

Enhancement of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA amplification in a Simian virus 40-transformed Chinese hamster cell line by 3-aminobenzamide.

A Simian virus 40-transformed Chinese hamster cell line (CO 60) amplifies integrated viral DNA sequences as a response to treatment with a variety of carcinogens. To study a possible involvement of poly(ADP-ribose) synthesis, DNA amplification was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), an alkylating carcinogen that strongly stimulates poly(ADP-ribose) synthesis. In the presence of 3-aminobenzamide (3AB) (2 mM), a competitive inhibitor of poly(ADP-ribose) polymerase, MNNG-induced amplification was increased two to six times the level induced by MNNG alone.

[Demonstration and organizational structure of the DNA of human papillomaviruses in laryngeal and hypopharyngeal carcinomas].

Thirty biopsy specimens from various histological types of human carcinomas of the larynx and hypopharynx were analysed for the presence of human papillomavirus (HPV) DNA: DNA from the individual specimens were tested for the presence of homologous sequences to HPV genotypes 1, 2, 4, 8, 9, 10, 11, 13, 16 and 18. One squamous cell carcinoma of the hypopharynx (postcricoideal area) contained multiple copies of DNA hybridizing under stringent conditions with HPV 16 DNA. The latter DNA has been found to be frequently associated with human genital cancer.