scholarly journals Identification of Six Putative Novel Human Papillomaviruses (HPV) and Characterization of Candidate HPV Type 87

2001 ◽  
Vol 75 (23) ◽  
pp. 11913-11919 ◽  
Author(s):  
Stefano Menzo ◽  
Alessia Monachetti ◽  
Caterina Trozzi ◽  
Andrea Ciavattini ◽  
Guido Carloni ◽  
...  

ABSTRACT Six putative novel human papillomavirus (HPV) types were detected by using general primers for a conserved L1 HPV region in patients examined in gynecologic centers. One of the isolates, detected in samples from 4 patients with koilocytic atypia at cervical cytology (3 of whom were also infected with human immunodeficiency virus type 1), was completely sequenced, identified as a new HPV genotype, and designated candidate HPV87 (candHPV87) by the Reference Center for Human Papillomavirus. candHPV87 shows the classic HPV genome organization and the absence of a functional E5 coding region. Phylogenetic analysis documented that thecandHPV87 genome clusters within the A3 group of HPVs, together with HPV61, HPV72, HPV83, HPV84 and candHPV86, which have been completely sequenced, and a number of other putative novel genotypes (two of which are described in this work), which have been partially characterized. To address the growth-enhancing potential of candHPV87, the E6 and E7 putative coding regions were cloned and expressed in tissue cultures. The data indicate that both proteins stimulate cell division in tissue cultures more than those of low-risk HPVs, though not as much as those of HPV16. Taken together, the clinical, molecular, and biological data suggest that the novel papillomavirus characterized in the present study is a low- to intermediate-risk HPV.

2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.


2021 ◽  
Vol 21 (1) ◽  
pp. 254-62
Author(s):  
Lucy Wanja Karani ◽  
Stanslaus Musyoki ◽  
Robert Orina ◽  
Christopher Khayeka-Wandabwa ◽  
Benuel Nyagaka

Background: Co-infection of High Risk Human Papillomavirus (HR-HPV) and HIV is thought to favour initiation of intraepithelial squamous cell lesion and subsequent progression to cervical carcinoma. Objectives: Evaluation of cytological physiognomies in relation to possible age influence and the genotype distribution of human papillomaviruses among HPV/HIV co-infected and HPV monoinfected women in Kisii, Kenya. Methods: The case-control study enrolled 42 HPV/HIV co-infected and 42 HPV monoinfected women. Cervical swabs were collected in ThinPrep vials for HPV tying and cytological analysis. HPV subtypes were assayed by Xpert® HPV system (GXHPV-CE-10). Results: Mono-infected women aged 30-39 years had the highest proportion of low grade squamous intraepithelial lesion (LSIL) at 14 (16.67%) while the co-infected aged 50-59 years had the highest proportion of high grade squamous intraepi- thelial lesion (HSIL) at 9 (10.71%). HPV-16 genotype was the most predominant and it increased with age rise. Older coin- fected and mono-infected women (>40 years) had HSIL and LSIL as the most predominant cytological grade respectively. Conclusion: The predominance of HPV-16 and HPV-18/45 genotypes in the study setting is a consideration that would benefit targeted prophylactic vaccination programs. HPV testing and cervical cancer screening for young and older women on a regular basis ought to be reinforced. Keywords: Human immunodeficiency virus (HIV); Human Papillomavirus (HPV); co-infection; genotype; cytology.


2005 ◽  
Vol 25 (14) ◽  
pp. 6247-6258 ◽  
Author(s):  
Huifang M. Zhang ◽  
Ji Yuan ◽  
Paul Cheung ◽  
David Chau ◽  
Brian W. Wong ◽  
...  

ABSTRACT Gamma interferon-inducible protein 10 (IP10) is a member of the CXC family of chemokines. By differential mRNA display, we have demonstrated the upregulation of IP10 in coxsackievirus B3 (CVB3)-infected mouse hearts. Functional characterization of the IP10 gene in IP10-transfected Tet-On HeLa cells has found that IP10 induced cell apoptosis and inhibited viral replication. In the characterization of the IP10-induced apoptotic pathway, we found that overexpression of IP10 upregulated p53 and resulted in altered expression of p53-responsive genes such as the p21Cip1, p27kip1, NF-κB, Bax, and PUMA genes and the mitochondrial translocation of Bax. However, transduction of the IP10 cells with adenovirus expressing dominant negative p53 not only ablated p53-triggered gene expression but also abolished IP10-induced apoptosis and restored CVB3 replication to the control levels. These data suggest a novel mechanism by which IP10 inhibits viral replication through the induction of host cell death via a p53-mediated apoptotic pathway. We also found that constantly high-level expression of p53 in these tumor cells is attributed to the IP10-induced suppression of human papillomavirus E6 and E7 oncogene expression. Taken together, these data reveal not only a previously unrecognized link between chemokine IP10 and p53 in antiviral defense but also a mechanism by which IP10 inhibits tumor cell growth.


1991 ◽  
Vol 1 (4) ◽  
pp. 209-219 ◽  
Author(s):  
Jean C. Kridl ◽  
David W. McCarter ◽  
Ronald E. Rose ◽  
Donna E. Scherer ◽  
Deborah S. Knutzon ◽  
...  

AbstractAn expressed napin storage protein gene fromBrassica rapa, BcNA1, has been cloned and sequenced. The gene is a member of a family of four to seven napin genes inB. rapaand is highly expressed in developing seeds. An expression cassette containing the DNA flanking the napin coding region of BcNA1 has been engineered and demonstrated to function appropriately, as compared with the gene's endogenous expression, in transgenic rapeseed using the β-glucuronidase reporter gene. TheB. rapaBcNA1 gene and aB. napusnapin gene, gNa, share extremely high nucleotide homology not only throughout their coding regions, but over a DNA locus comprising 4.3 kb. We suggest the gNa gene was contributed by the originalB. rapaprogenitor of the amphidiploidB. napus.


2003 ◽  
Vol 10 (3) ◽  
pp. 431-438 ◽  
Author(s):  
Jennifer E. Cameron ◽  
Isaac V. Snowhite ◽  
Anil K. Chaturvedi ◽  
Michael E. Hagensee

ABSTRACT Serological assays are valuable tools for studies of the epidemiology of human papillomaviruses (HPVs). The efficacy of a less invasive oral-fluid assay for detection of HPV antibodies was examined. Matched serum, saliva, and oral mucosal transudate (OMT) specimens collected from 150 human immunodeficiency virus-seropositive patients were tested for immunoglobulin G antibodies against HPV-6 and HPV-11 combined (HPV-6/11) and HPV-16 capsids. Antibodies to HPV were detected in both types of oral specimens. Seroprevalence rates were 55% for HPV-6/11 and 37% for HPV-16, whereas oral prevalence rates were significantly lower (for HPV-6/11 in saliva, 31%, and in OMT, 19%; for HPV-16 in saliva, 19%, and in OMT, 17%). HPV antibody detection in OMT more accurately reflected the presence of antibodies in serum than did HPV antibody detection in saliva. More stringent saliva assay cutpoints yielded stronger associations between oropositivity and seropositivity; less stringent OMT cutpoints yielded stronger associations between oropositivity and seropositivity. Although HPV antibodies were detected in oral fluids, further optimization of the assay is necessary before oral-fluid testing can be implemented as a reliable alternative to serum testing for HPV.


1998 ◽  
Vol 88 (9) ◽  
pp. 442-445 ◽  
Author(s):  
R Meberg ◽  
E Kenyon ◽  
R Bierman ◽  
L Loveland ◽  
P Barbosa

Plantar verrucae, caused by human papillomavirus (HPV), are commonly found in patients who have tested positive for the antibodies to human immunodeficiency virus (HIV). A better understanding of the characteristics of plantar verrucae in HIV+ patients in needed. A pilot study was conducted concentrating on three characteristics--the size, the number, and the clinical type--of verrucae present in this population. These parameters were studied in HIV+ and HIV- populations, and they were evaluated in relation to the CD4 levels of HIV+ individuals. The HIV+ individuals presented with plantar verrucae that were larger and more numerous than those found in HIV- individuals. The HIV+ population presented with all three clinical types of plantar verrucae and had significantly more mosaic-type warts than did HIV- individuals. The three characteristics did not correlate with CD4 cell counts, suggesting that the severity and extent of HPV infection do not depend on the level of immunosuppression of the HIV+ patient.


2000 ◽  
Vol 74 (16) ◽  
pp. 7284-7297 ◽  
Author(s):  
Simon N. Stacey ◽  
Deborah Jordan ◽  
Andrew J. K. Williamson ◽  
Michael Brown ◽  
Joanna H. Coote ◽  
...  

ABSTRACT Human papillomaviruses (HPV) are unique in that they generate mRNAs that apparently can express multiple proteins from tandemly arranged open reading frames. The mechanisms by which this is achieved are uncertain and are at odds with the basic predictions of the scanning model for translation initiation. We investigated the unorthodox mechanism by which the E6 and E7 oncoproteins from human papillomavirus type 16 (HPV-16) can be translated from a single, bicistronic mRNA. The short E6 5′ untranslated region (UTR) was shown to promote translation as efficiently as a UTR from Xenopusβ-globin. Insertion of a secondary structural element into the UTR inhibited both E6 and E7 expression, suggesting that E7 expression depends on ribosomal scanning from the 5′ end of the mRNA. E7 translation was found to be cap dependent, but E6 was more dependent on capping and eIF4F activity than E7. Insertion of secondary structural elements at various points in the region upstream of E7 profoundly inhibited translation, indicating that scanning was probably continuous. Insertion of the E6 region between Renilla and firefly luciferase genes revealed little or no internal ribosomal entry site activity. However when E6 was located at the 5′ end of the mRNA, it permitted over 100-fold-higher levels of downstream cistron translation than did the Renilla open reading frame. Internal AUGs in the E6 region with strong or intermediate Kozak sequence contexts were unable to inhibit E7 translation, but initiation at the E7 AUG was efficient and accurate. These data support a model in which E7 translation is facilitated by an extreme degree of leaky scanning, requiring the negotiation of 13 upstream AUGs. Ribosomal initiation complexes which fail to initiate at the E6 start codon can scan through to the E7 AUG without initiating translation, but competence to initiate is achieved once the E7 AUG is reached. These findings suggest that the E6 region of HPV-16 comprises features that sponsor both translation of the E6 protein and enhancement of translation at a downstream site.


2014 ◽  
Vol 104 (11) ◽  
pp. 1241-1250 ◽  
Author(s):  
María Bergua ◽  
Marisol Luis-Arteaga ◽  
Fernando Escriu

The variability and genetic structure of Alfalfa mosaic virus (AMV) in Spain was evaluated through the molecular characterization of 60 isolates collected from different hosts and different geographic areas. Analysis of nucleotide sequences in four coding regions—P1, P2, movement protein (MP), and coat protein (CP)—revealed a low genetic diversity and different restrictions to variation operating on each coding region. Phylogenetic analysis of Spanish isolates along with previously reported AMV sequences showed consistent clustering into types I and II for P1 and types I, IIA, and IIB for MP and CP regions. No clustering was observed for the P2 region. According to restriction fragment length polymorphism analysis, the Spanish AMV population consisted of seven haplotypes, including two haplotypes generated by reassortment and one involving recombination. The most frequent haplotypes (types for P1, MP, and CP regions, respectively) were I-I-I (37%), II-IIB-IIB (30%), and one of the reassortants, II-I-I (17%). Distribution of haplotypes was not uniform, indicating that AMV population was structured according to the geographic origin of isolates. Our results suggest that agroecological factors are involved in the maintenance of AMV genetic types, including the reassortant one, and in their geographic distribution.


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