Infectious titres of human papillomaviruses (HPVs) in patient lesions, methodological considerations in evaluating HPV infectivity and implications for the efficacy of high-level disinfectants

Ozbun, Michelle A.; Bondu, Virginie; Patterson, Nicole; Sterk, Rosa T.; Waxman, Alan G.; Bennett, Erica C.; McKee, Rohini; Sharma, Ankur; Yarwood, Jeremy; Rogers, Marc; Eichenbaum, Gary

doi:10.1016/j.ebiom.2020.103165

Cited by 13 publications

(19 citation statements)

References 36 publications

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“…Prior to experimentation, all virus stocks were characterized for virus capsid content, pseudogenome (via a luciferase expression plasmid) or HPV genome levels (viral genome equivalents [VGE]), and susceptibility to neutralization by characterized monoclonal antibodies as we previously detailed ( 47 ) (see Fig. S1 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, these assays cannot discern whether PS treatment leads to infection of fewer cells or whether the same number of cells are infected but express lower levels of luciferase or viral mRNAs. To address this issue, we used a cell-based focus-forming assay that evaluates infection using RNA in situ hybridization (RNA-ISH) detection of HPV mRNA as we reported previously ( 47 ). HaCaT cells were pretreated with PS for 1 h and exposed to raft tissue-derived HPV31.…”

Section: Resultsmentioning

confidence: 99%

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Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn VitroandIn Vivo

Young

Abidine

Gómez-Martínez

et al. 2022

Antimicrob Agents Chemother

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Human papillomavirus (HPV) infections are transmitted through sexual or other close contact and are etiologically associated with epithelial warts, papillomas, and intraepithelial lesions that may progress to cancer. Indeed, 4.8% of the global cancer burden is linked to HPV infection. Highly effective vaccines protect against two to nine of the most medically important HPV genotypes; yet vaccine uptake is inadequate and/or cost prohibitive in many settings. With HPV-related cancer incidence expected to rise over the coming decades, there is a need for effective HPV microbicides. Herein we demonstrate the strong inhibitory activity of the heparin-neutralizing drug protamine sulfate (PS) against HPV infection. Pretreatment of cells with PS greatly reduced infection regardless of HPV genotype or virus source. Vaginal application of PS prevented infection of the murine genital tract by HPV pseudovirions. Time-of-addition assays where PS was added to cells before infection, during infection, or after viral attachment demonstrated strong inhibitory activities on early infection steps. No effect on virus infection was found for cell lines deficient in heparan sulfate expression, suggesting that PS binds to heparan sulfate on the cell surface. Consistent with this, prophylactic PS exposure prevented viral attachment, including under low pH conditions akin to the human vaginal tract. Our findings suggest PS acts dually to prevent HPV infection: prophylactic treatment prevents HPV attachment to host cells and post-attachment administration alters viral entry. Clinical trials are warranted to determine whether protamine-based products are effective as topical microbicides against genital HPVs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn VitroandIn Vivo

Young

Abidine

Gómez-Martínez

et al. 2022

Antimicrob Agents Chemother

Self Cite

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“…Worldwide, the most common types of HPV in cervical-uterine cancer are: 16 (57%), 18 (16%), 58 (5%), 33 (5%), 45 (5%), 31 (4%), 52 (3%), and 35 (2%) [ 10 ]. Types 16, 18, and 45 represent a greater or equal proportion of cervical cancer infections.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Resistive DNA Biosensor for the Detection of HPV Type 16

et al. 2021

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In this work, a low-cost and rapid electrochemical resistive DNA biosensor based on the current relaxation method is described. A DNA probe, complementary to the specific human papillomavirus type 16 (HPV-16) sequence, was immobilized onto a screen-printed gold electrode. DNA hybridization was detected by applying a potential step of 30 mV to the system, composed of an external capacitor and the modified electrode DNA/gold, for 750 µs and then relaxed back to the OCP, at which point the voltage and current discharging curves are registered for 25 ms. From the discharging curves, the potential and current relaxation were evaluated, and by using Ohm’s law, the charge transfer resistance through the DNA-modified electrode was calculated. The presence of a complementary sequence was detected by the change in resistance when the ssDNA is transformed in dsDNA due to the hybridization event. The target DNA concentration was detected in the range of 5 to 20 nM. The results showed a good fit to the regression equation ΔRtotal(Ω)=2.99 × [DNA]+81.55, and a detection limit of 2.39 nM was obtained. As the sensing approach uses a direct current, the electronic architecture of the biosensor is simple and allows for the separation of faradic and nonfaradaic contributions. The simple electrochemical resistive biosensor reported here is a good candidate for the point-of-care diagnosis of HPV at a low cost and in a short detection time.

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“…In two articles of EBioMedicine, the authors presented a very detailed and controlled set of experiments to determine the efficacy of ortho-phthalaldehyde (OPA), hypoclorite and hydrogen peroxide in inactivating PVs particles from experimental models, including quasivirions, xenografts, raft cultures and Mus musculus PV type 1 (MmuPV1) induced-lesions in mice. Besides, they included the analysis of HPVs virions retrieved from recurrent respiratory papillomas, anal warts and cervical lesions from patients with hrHPV [5,6].…”

mentioning

confidence: 99%

“…The study by Ozbun and colleagues described a precise workflow to determine the efficacy of disinfectants against HPV virions that may remain on surfaces [5]. This is important to prevent the transmission of different HPV types by fomites in nosocomial/health care settings.…”

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confidence: 99%

New approaches for infective HPV detection, quantification and inactivation: Preventing accidental virus transmission in medical settings

Boccardo

2021

EBioMedicine

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Infectious titres of human papillomaviruses (HPVs) in patient lesions, methodological considerations in evaluating HPV infectivity and implications for the efficacy of high-level disinfectants

Cited by 13 publications

References 36 publications

Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn VitroandIn Vivo

Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn VitroandIn Vivo

Electrochemical Resistive DNA Biosensor for the Detection of HPV Type 16

New approaches for infective HPV detection, quantification and inactivation: Preventing accidental virus transmission in medical settings

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