scholarly journals The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

2015 ◽  
Vol 59 (9) ◽  
pp. 5250-5259 ◽  
Author(s):  
Valeria Cagno ◽  
Manuela Donalisio ◽  
Antonella Bugatti ◽  
Andrea Civra ◽  
Roberta Cavalli ◽  
...  
Keyword(s):  
Cell Surface ◽  
Viral Infections ◽  
Human Papillomaviruses ◽  
Sexually Transmitted ◽  
Human Papillomavirus 16 ◽  
Virus Attachment ◽  
Hpv Types ◽  
Heparan Sulfates ◽  
Further Development ◽  
Topical Microbicide

ABSTRACTThe agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.

scholarly journals Identification of a Dendrimeric Heparan Sulfate-Binding Peptide That Inhibits Infectivity of Genital Types of Human Papillomaviruses

2010 ◽  
Vol 54 (10) ◽  
pp. 4290-4299 ◽  
Author(s):  
Manuela Donalisio ◽  
Marco Rusnati ◽  
Andrea Civra ◽  
Antonella Bugatti ◽  
Donatella Allemand ◽  
...  
Keyword(s):  
Viral Infections ◽  
Biological Properties ◽  
Human Papillomaviruses ◽  
Sexually Transmitted ◽  
Virus Attachment ◽  
Peptide Dendrimers ◽  
Heparan Sulfates ◽  
Further Development ◽  
Topical Microbicide

ABSTRACT Peptide dendrimers consist of a peptidyl branching core and/or covalently attached surface functional units. They show a variety of biological properties, including antiviral activity. In this study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was evaluated for in vitro activity against human papillomaviruses (HPVs). The peptide dendrimer SB105-A10 was found to be a potent inhibitor of genital HPV types (i.e., types 16, 18, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 2.8 and 4.2 μg/ml (0.59 and 0.88 μM), and no evidence of cytotoxicity was observed. SB105-A10 interacts with immobilized heparin and with heparan sulfates exposed on the cell surface, most likely preventing virus attachment. The findings from this study indicate SB105-A10 to be a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.

scholarly journals Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Rashi Yadav ◽  
Lukai Zhai ◽  
Ebenezer Tumban
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Hpv Vaccine ◽  
Genital Warts ◽  
Human Papillomaviruses ◽  
Target Antigen ◽  
Sexually Transmitted ◽  
Virus Like Particle ◽  
Protective Antibodies ◽  
Hpv Types

Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further.

scholarly journals In Vitro Microbicidal Activities of Cecropin Peptides D2A21 and D4E1 and Gel Formulations Containing 0.1 to 2% D2A21 against Chlamydia trachomatis

2002 ◽  
Vol 46 (1) ◽  
pp. 34-41 ◽  
Author(s):  
L. M. Ballweber ◽  
J. E. Jaynes ◽  
W. E. Stamm ◽  
M. F. Lampe
Keyword(s):  
Chlamydia Trachomatis ◽  
Initial Exposure ◽  
Sexually Transmitted ◽  
Ultrastructural Studies ◽  
Ph Values ◽  
Further Development ◽  
Gel Formulations ◽  
Powerful Strategy ◽  
Topical Microbicide

ABSTRACT Topically applied microbicides that eradicate pathogens at the time of initial exposure represent a powerful strategy for the prevention of sexually transmitted infections. To aid in the further development of an effective topical microbicide, we assessed the minimum cidal concentration (MCC) of two cecropin peptides, D2A21 and D4E1, and gel formulations containing 0.1 to 2% D2A21 against Chlamydia trachomatis in vitro. The MCC of peptide D2A21was 5 μM (18.32 μg/ml), and that of peptide D4E1 was 7.5 μM (21.69 μg/ml). The MCC of gel formulations containing 2% D2A21 was 0.2 mM (0.7 mg/ml), and that of gel formulations containing 0.5% D2A21 was 0.2 mM (0.7 mg/ml). There was no significant variation in the results when two different C. trachomatis strains were tested, and the addition of 10% human blood did not significantly alter the MCCs. pH values above and below 7 reduced the activity of the D2A21 peptide alone, but the MCC of the 2% D2A21 gel formulation was only slightly altered at the various pHs tested. Ultrastructural studies indicated that C. trachomatis membranes were disrupted after D2A21 exposure, resulting in leakage of the cytoplasmic contents. These in vitro results suggest that these cecropin peptides may be an effective topical microbicide against C. trachomatis and support the need for further evaluation.

scholarly journals Detection of Human Papillomaviruses DNA in paired peripheral blood and cervix samples patients with cervical lesions and healthy individuals

2021 ◽  
Author(s):  
Kamylla Conceicao Gomes Nascimento ◽  
Elyda Goncalves Lima ◽  
Barbara Simas Chagas ◽  
Zhilbelly Mota Nunes ◽  
Marconi Rego Barros Junior ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Healthy Individuals ◽  
Cervical Lesions ◽  
Hpv16 E6 ◽  
Hpv Dna ◽  
Sexually Transmitted ◽  
Standard Procedures ◽  
Hpv Types

This study evaluated the presence of HPV DNA in the cervix and peripheral blood of women with cervical intraepithelial neoplasia (CIN I, II, and III) and healthy individuals. Overall, 139 paired peripheral blood and cervix samples of healthy women and women with CIN I, II, and III (n= 68) were tested for HPV DNA by using standard procedures. PCR-sequencing determined HPV types. Quantification of HPV16 E6 and E2 genes was performed to determine viral load and physical state. HPV DNA was detected in the cervix (21.1% in healthy individuals; 48.8-55.5% in CIN patients), blood (46.4% in healthy individuals; 44.1-77.7% in CIN patients), and paired peripheral blood and cervix samples (24% in healthy individuals; 32.5-44.4% in CIN patients). The most frequent types found in the cervix were HPV16, 18, 31, 33, 58, and 70, while HPV16, 18, 33, 58, and 66 were the most frequent types found in the blood. HPV DNA in the cervix was associated with previous sexually transmitted infections (STIs) (P=0.023; OR: 2.978; CI:1.34-7.821), HPV DNA in the blood (P=0.000; OR: 3.369; CI:3.700-18.540), and cervical lesions (CIN I/II or III) (P=0.001; OR: 3.369; CI:1.634-6.945). Binomial Logistic regression showed that HPV DNA in the blood (P=0.000; OR: 9.324; CI:3.612-24.072) and cervical lesions (P=0.011; OR: 3.622; CI:1.338-9.806) were associated with HPV DNA in the cervix. However, we did not find an association between HPV DNA in blood and cervical lesions (P=0.385). Our results showed that, although there is an association between HPV DNA in the cervix with HPV DNA in blood, only HPV DNA found in the cervix was associated with cervical lesions.

scholarly journals Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

2020 ◽  
Vol 21 (13) ◽  
pp. 4675 ◽  
Author(s):  
Irene Ramos ◽  
Konstantinos Stamatakis ◽  
Clara L. Oeste ◽  
Dolores Pérez-Sala
Keyword(s):  
Cell Surface ◽  
Posttranslational Modifications ◽  
Cell Activation ◽  
Viral Infections ◽  
Cell Types ◽  
Special Focus ◽  
Intermediate Filament Protein ◽  
Virus Attachment ◽  
Numerous Cell ◽  
And Migration

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed.

scholarly journals Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

2020 ◽  
Author(s):  
Irene Ramos ◽  
Konstantinos Stamatakis ◽  
Clara L. Oeste ◽  
Dolores Pérez-Sala
Keyword(s):  
Cell Surface ◽  
Posttranslational Modifications ◽  
Cell Activation ◽  
Viral Infections ◽  
Cell Types ◽  
Special Focus ◽  
Intermediate Filament Protein ◽  
Virus Attachment ◽  
Numerous Cell ◽  
And Migration

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

scholarly journals Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers

2021 ◽  
Vol 9 (10) ◽  
pp. 2092
Author(s):  
Helen Espinoza ◽  
Kim T. Ha ◽  
Trang T. Pham ◽  
J. Luis Espinoza
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Sexually Transmitted ◽  
Individual Susceptibility ◽  
Hpv Types ◽  
Genetic And Environmental Factors ◽  
The Individual

Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers. Previous studies have quantified that heritability, in the form of genetic variants, common in the general population, is implicated in nearly 30% of cervical cancers and a large number of studies conducted across various populations have identified genetic variants that appear to be associated with genes that predispose or protect the host to HPV infections thereby affecting individual susceptibility to HPV-associated cancers. In this article, we provide an overview of gene association studies on HPV-associated cancers with emphasis on genome-wide association study (GWAS) that have identified novel genetic factors linked to HPV infection or HPV-associated cancers.

scholarly journals Inactivation of Polyomavirus SV40 as Surrogate for Human Papillomaviruses by Chemical Disinfectants

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2207
Author(s):  
Martin Hufbauer ◽  
Ulrike Wieland ◽  
Jürgen Gebel ◽  
Jochen Steinmann ◽  
Baki Akgül ◽  
...  
Keyword(s):  
Contact Time ◽  
No Reduction ◽  
Virus Transmission ◽  
Human Papillomaviruses ◽  
Transmission Route ◽  
Virucidal Activity ◽  
Dna Viruses ◽  
Sexually Transmitted ◽  
Hpv Types ◽  
Ammonium Compounds

Human papillomaviruses (HPV) are non-enveloped DNA viruses infecting cutaneous and mucosal squamous epithelia. Sexually transmitted HPV-types that are carcinogenic to humans such as HPV16 can induce cervical and other anogenital cancers. Virus transmission through fomites such as inadequately disinfected gynecological equipment is a further potential transmission route. Since HPV cannot be easily grown in cell culture, polyomavirus SV40 has been used as a surrogate virus when testing the virucidal activity of chemical disinfectants. So far, studies that have compared the virucidal activity of different disinfectants against HPV and SV40 are lacking. Here, we evaluated the susceptibility of HPV16 pseudovirus and SV40 to seven active biocidal substances using quantitative suspension tests. Ethanol, glutaraldehyde (GTA), dodecyldipropylentriamin (DPTA), and ortho-phthalaldehydes (OPA) were able to reduce the infectivity of HPV16 pseudovirus >99.99% after 5 min. In contrast, isopropanol, peracetic acid (PAA), and quaternary ammonium compounds with alkylamines (QAC) only led to a slight or no reduction in infectivity. Concerning SV40, only GTA (60 min contact time), PAA, and OPA had virus-inactivating effects. In conclusion, the virucidal activity of three out of seven disinfectants tested was different for HPV16 pseudovirus and SV40. In this study, SV40 was shown to be a reliable surrogate virus for HPV when testing isopropanol-, GTA-, QAC-, and OPA-based disinfectants.

Papillomavirus infection and reproduction

2020 ◽  
Vol 75 (3) ◽  
pp. 189-195
Author(s):  
Vladislav I. Krasnopolsky ◽  
Nina V. Zarochentseva ◽  
Ksenia V. Krasnopolskaya ◽  
Yulia N. Bashankaeva ◽  
Varvara S. Kuzmicheva
Keyword(s):  
Human Papillomavirus ◽  
Hpv Vaccination ◽  
Carcinogenic Risk ◽  
Human Papillomaviruses ◽  
World Health ◽  
Sexually Transmitted ◽  
Associated Diseases ◽  
Trophoblastic Cells ◽  
Papillomavirus Infection ◽  
Health Organization

The purpose of the review a synthesis of research data on the role of human papillomavirus infection in the reproductive health of women and men. Key Points. Human papillomavirus (HPV) is one of the most common sexually transmitted viruses worldwide. According to the World Health Organization, HPV is the main cause of the development of HPV-associated diseases among both women and men. Viruses are subdivided into HPV with low carcinogenic risk, which cause benign warts, and HPV with high carcinogenic risk, which cause cancer. Different types of human papillomaviruses depending on their characteristic tropism, are divided into skin and mucous types. Viral infection in men leads to a decrease in the quality of sperm (for example, asthenozoospermia) due to apoptosis in sperm cells and due to the development of antisperm immunity. A negative viral effect on the fertility of women is manifested in an increase in the frequency of spontaneous miscarriages and a premature rupture of the amniotic membranes during pregnancy. There is evidence that HPV decreases the number of trophoblastic cells and abnormal trophoblastic-endometrial adhesion is also observed. In trophoblastic cells transfected with high-risk HPV, the level of apoptosis increases. HPV vaccination is safe, and the results show not only protection against HPV-associated diseases in women and men, but also a reduction of gestational complications, reduced preterm birth rates and the protection of newborns from infection.

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