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Viruses
Special Issues
Immune Responses to Papillomavirus Infections
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Immune Responses to Papillomavirus Infections

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 11840

Special Issue Editors

Dr. Jiafen Hu

E-Mail Website
Guest Editor
Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Interests: papillomavirus; innate immunity; adaptive immunity
Dr. Vivien Béziat

E-Mail Website
Guest Editor
Imagine Institute, University of Paris, Paris, France
Interests: immunology; genetics; papillomaviruses; NK cell

Special Issue Information

Dear Colleagues,

Human papillomavirus (HPV) infection is the most common sexually transmitted disease that causes approximately 5% of human cancers. Current prophylactic vaccines are effective at preventing HPV infections but provided no therapeutic effect on pre-existing HPV infections. Intriguingly, most HPV (about 90%) infections are cleared by hosts within 1-2 years after exposure. Understanding host control of HPV infections will potentially shed light on the development of novel therapy for HPV associated diseases and cancers.

Innate and adaptive immunity have contributed to recognize and fight HPV infections. However, HPV has several mechanisms for circumventing the immune responses. Frist, HPV uses rare codons for its genes. Therefore, most genes are expressed in a level undetectable by the immune system. Second, HPV infects, and reproduces in skin and mucosal keratinocytes, which are distant from immune centers and have a naturally short lifespan. The naturally short lifespan of the keratinocytes avoids the need for the virus to destroy these infected cells, which would trigger inflammation and immune responses. Third, HPV downregulates the expression of anti-viral interferon genes which leads to prolonged viral infections, a risk factor for HPV associated cancer development.

The current issue covers research relating to how the immune system effectively clear papillomavirus infections, and what immune responses are key factors in this optimum outcome. We would like to invite you to share your recent findings or perspectives on host immunity to papillomavirus, including but not limited to innate and adaptive immune responses in preclinical models and human studies. 

Dr. Jiafen Hu
Dr. Vivien Béziat
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • papillomavirus
  • HPV
  • immune responses
  • infections
  • models

Published Papers (8 papers)

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Research

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13 pages, 3006 KiB  
Article
Immunological Response against Breast Lineage Cells Transfected with Human Papillomavirus (HPV)
by Daffany Luana Santos, Bianca de França São Marcos, Georon Ferreira de Sousa, Leonardo Carvalho de Oliveira Cruz, Bárbara Rafaela da Silva Barros, Mariane Cajuba de Britto Lira Nogueira, Talita Helena de Araújo Oliveira, Anna Jessica Duarte Silva, Vanessa Emanuelle Pereira Santos, Cristiane Moutinho Lagos de Melo and Antonio Carlos de Freitas
Viruses 2024, 16(5), 717; https://0-doi-org.brum.beds.ac.uk/10.3390/v16050717 (registering DOI) - 30 Apr 2024
Abstract
Breast cancer is the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. Despite the detection of HPV in breast carcinomas, the virus’s activity against this type of cancer remains controversial. HPV infection [...] Read more.
Breast cancer is the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. Despite the detection of HPV in breast carcinomas, the virus’s activity against this type of cancer remains controversial. HPV infection promotes remodeling of the host’s immune response, resulting in an immunosuppressive profile. This study assessed the individual role of HPV oncogenes in the cell line MDA-MB-231 transfected with the E5, E6, and E7 oncogenes and co-cultured with peripheral blood mononuclear cells. Immunophenotyping was conducted to evaluate immune system modulation. There was an increase in CD4+ T cell numbers when compared with non-transfected and transfected MDA-MB-231, especially in the Treg profile. Pro-inflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17, were impaired by transfected cells, and a decrease in the cytolytic activity of the CD8+ and CD56+ lymphocytes was observed in the presence of HPV oncogenes, mainly with E6 and E7. The E6 and E7 oncogenes decrease monocyte expression, activating the expected M1 profile. In the monocytes found, a pro-inflammatory role was observed according to the cytokines released in the supernatant. In conclusion, the MDA-MB-231 cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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11 pages, 571 KiB  
Article
Effect of a Second Pregnancy on the HPV Serology in Mothers Followed Up in the Finnish Family HPV Study
by Helmi Suominen, Nelli Suominen, Kari Syrjänen, Tim Waterboer, Seija Grénman, Stina Syrjänen and Karolina Louvanto
Viruses 2023, 15(10), 2109; https://0-doi-org.brum.beds.ac.uk/10.3390/v15102109 - 18 Oct 2023
Viewed by 1011
Abstract
The impact of pregnancy on human papillomavirus (HPV) natural antibody levels is not fully understood. We tested the seroprevalence and levels of HPV 6, 11, 16, 18 and 45 antibodies at different time points among 89 women with a second pregnancy and 238 [...] Read more.
The impact of pregnancy on human papillomavirus (HPV) natural antibody levels is not fully understood. We tested the seroprevalence and levels of HPV 6, 11, 16, 18 and 45 antibodies at different time points among 89 women with a second pregnancy and 238 nonpregnant women during their 36-month followup. All participants were unvaccinated for HPV and pregnant at the enrollment of the study. Serum samples were collected from the mothers at baseline and at the 12-month, 24-month, and 36-month followup visits. No statistically significant differences in mean antibody levels were observed in women who developed a second pregnancy compared to their nonpregnant counterparts. Between these two groups, statistically significant differences in serostatus were observed, particularly if the second pregnancy was ongoing at the 24-month timepoint. Accordingly, women with a second pregnancy were more likely to be seronegative for HPV 6, 11, 18, and 45 as compared to the nonpregnant women, the reverse being true for HPV16. In contrast, the women with an ongoing second pregnancy showed a higher prevalence of HPV16 seropositivity at the 36-month followup. These data suggest that a second pregnancy does not seem to have a major impact on the levels of HPV antibodies, but it might influence the serological outcomes. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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12 pages, 1202 KiB  
Article
The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2
by Mayumi Saito, Aarthi Rajesh, Carrie Innes, Rachael van der Griend, Peter Fitzgerald, Bryony Simcock, Peter Sykes and Merilyn Hibma
Viruses 2023, 15(9), 1953; https://0-doi-org.brum.beds.ac.uk/10.3390/v15091953 - 19 Sep 2023
Viewed by 1044
Abstract
High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial [...] Read more.
High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV ‘other’). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV ‘other’ lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV ‘other’ types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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14 pages, 2119 KiB  
Article
Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil
by Luana Lorena Silva Rodrigues, José Henrique Pilotto, Katrini Guidolini Martinelli, Alcina F. Nicol, Vanessa Salete De Paula, Tarik Gheit, Nathália Silva Carlos Oliveira, Carlos Silva-de-Jesus, Vikrant V. Sahasrabuddhe, Diane M. Da Silva, W. Martin Kast, Justin Hardick, Charlotte A. Gaydos and Mariza Gonçalves Morgado
Viruses 2023, 15(6), 1328; https://0-doi-org.brum.beds.ac.uk/10.3390/v15061328 - 06 Jun 2023
Viewed by 1516
Abstract
The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study [...] Read more.
The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study was performed with 112 HIV-uninfected and 41 HIV-infected nonindigenous women. Anal and cervical scrapings were collected and analyzed for HPV, Chlamydia trachomatis (CT), Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2). The Kappa test evaluated the concordance between anal and genital infections. The overall prevalence of anal HPV infection was 31.3% in HIV-uninfected and 97.6% in HIV-infected women. The most frequent anal high-risk HPV (hrHPV) types were HPV18 and HPV16 in HIV-uninfected women and HPV51, HPV59, HPV31, and HPV58 in HIV-infected women. Anal HPV75 Betapapillomavirus was also identified. Anal non-HPV STIs were identified in 13.0% of all participants. The concordance analysis was fair for CT, MG, and HSV-2, almost perfect agreement for NG, moderate for HPV, and variable for the most frequent anal hrHPV types. Thus, a high prevalence of anal HPV infection with moderate and fair concordance between anal and genital HPV and non-HPV STIs was observed in our study. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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15 pages, 322 KiB  
Article
Peripheral Blood T-lymphocyte Phenotypes in Mother-Child Pairs Stratified by the Maternal HPV Status: Persistent HPV16 vs. HPV-Negative: A Case-Control Study
by Helmi Suominen, Anna Paaso, Hanna-Mari Koskimaa, Seija Grénman, Kari Syrjänen, Stina Syrjänen and Karolina Louvanto
Viruses 2022, 14(12), 2633; https://0-doi-org.brum.beds.ac.uk/10.3390/v14122633 - 25 Nov 2022
Cited by 2 | Viewed by 1225
Abstract
Only few studies exist on the phenotype distribution of peripheral blood lymphocytes concerning persistent oral HPV infection. T-lymphocyte subsets were phenotyped in women who had persistent genital or oral HPV16 infection, using HPV-negative women as a reference group. A subset of 42 mothers [...] Read more.
Only few studies exist on the phenotype distribution of peripheral blood lymphocytes concerning persistent oral HPV infection. T-lymphocyte subsets were phenotyped in women who had persistent genital or oral HPV16 infection, using HPV-negative women as a reference group. A subset of 42 mothers and their children (n = 28), were stratified into two groups according to the mothers’ HPV status. PBMCs from previously cryopreserved venous samples were immunophenotyped by flow cytometry. Proportions of the CD4+ or CD8+ lymphocytes by their immunophenotype subsets were compared between HPV-positive and -negative mothers and their children. The mean rank distribution of CD8+ memory cells was significantly higher among mothers with persistent genital HPV16 infection. The median levels of both the antigen-presenting CD4+ cells and activated CD8+ cells were significantly lower in mothers with persistent oral HPV16 infection. When oral and genital HPV16-persistors were analyzed as a group, a marker of terminal effector cells was significantly increased as compared to HPV-negative women. Significantly higher levels of activated CD4+, CD8+ and circulating CD8+ memory cells were found among children whose mothers had persistent oral HPV16 infection. Persistent HPV16 infections are associated with changes in peripheral blood T-lymphocyte subsets. The mother’s persistent oral HPV16 infection possibly results in immune alterations in her offspring. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)

Review

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25 pages, 1223 KiB  
Review
Unraveling Immunological Dynamics: HPV Infection in Women—Insights from Pregnancy
by Carmen Elena Condrat, Dragos Cretoiu, Viorica Elena Radoi, Dana Mihaela Mihele, Mihaela Tovaru, Cristian Ioan Bordea, Silviu Cristian Voinea and Nicolae Suciu
Viruses 2023, 15(10), 2011; https://0-doi-org.brum.beds.ac.uk/10.3390/v15102011 - 27 Sep 2023
Viewed by 3005
Abstract
During pregnancy, hormonal and immune adaptations are vital for supporting the genetically distinct fetus during elevated infection risks. The global prevalence of HPV necessitates its consideration during pregnancy. Despite a seemingly mild immune response, historical gestational viral infections underscore its significance. Acknowledging the [...] Read more.
During pregnancy, hormonal and immune adaptations are vital for supporting the genetically distinct fetus during elevated infection risks. The global prevalence of HPV necessitates its consideration during pregnancy. Despite a seemingly mild immune response, historical gestational viral infections underscore its significance. Acknowledging the established HPV infection risks during pregnancy, our review explores the unfolding immunological changes in pregnant women with HPV. Our analysis aims to uncover strategies for safely modulating the immune system, mitigating adverse pregnancy consequences, and enhancing maternal and child health. This comprehensive narrative review delves into the existing knowledge and studies on this topic. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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23 pages, 2210 KiB  
Review
The Tumor-Specific Immune Landscape in HPV+ Head and Neck Cancer
by Jacob P. Conarty and Andreas Wieland
Viruses 2023, 15(6), 1296; https://0-doi-org.brum.beds.ac.uk/10.3390/v15061296 - 31 May 2023
Cited by 3 | Viewed by 2303
Abstract
Human papillomaviruses (HPVs) are the causative agent of several anogenital cancers as well as head and neck cancers, with HPV+ head and neck squamous cell carcinoma (HNSCC) becoming a rapidly growing public health issue in the Western world. Due its viral etiology and [...] Read more.
Human papillomaviruses (HPVs) are the causative agent of several anogenital cancers as well as head and neck cancers, with HPV+ head and neck squamous cell carcinoma (HNSCC) becoming a rapidly growing public health issue in the Western world. Due its viral etiology and potentially its subanatomical location, HPV+ HNSCC exhibits an immune microenvironment which is more inflamed and thus distinct from HPV-negative HNSCC. Notably, the antigenic landscape in most HPV+ HNSCC tumors extends beyond the classical HPV oncoproteins E6/7 and is extensively targeted by both the humoral and cellular arms of the adaptive immune system. Here, we provide a comprehensive overview of HPV-specific immune responses in patients with HPV+ HNSCC. We highlight the localization, antigen specificity, and differentiation states of humoral and cellular immune responses, and discuss their similarities and differences. Finally, we review currently pursued immunotherapeutic treatment modalities that attempt to harness HPV-specific immune responses for improving clinical outcomes in patients with HPV+ HNSCC. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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Other

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12 pages, 1758 KiB  
Opinion
The Chemokine CXCL14 as a Potential Immunotherapeutic Agent for Cancer Therapy
by Nicholas S. Giacobbi, Shreya Mullapudi, Harrison Nabors and Dohun Pyeon
Viruses 2024, 16(2), 302; https://0-doi-org.brum.beds.ac.uk/10.3390/v16020302 - 16 Feb 2024
Viewed by 846
Abstract
There is great enthusiasm toward the development of novel immunotherapies for the treatment of cancer, and given their roles in immune system regulation, chemokines stand out as promising candidates for use in new cancer therapies. Many previous studies have shown how chemokine signaling [...] Read more.
There is great enthusiasm toward the development of novel immunotherapies for the treatment of cancer, and given their roles in immune system regulation, chemokines stand out as promising candidates for use in new cancer therapies. Many previous studies have shown how chemokine signaling pathways could be targeted to halt cancer progression. We and others have revealed that the chemokine CXCL14 promotes antitumor immune responses, suggesting that CXCL14 may be effective for cancer immunotherapy. However, it is still unknown what mechanism governs CXCL14-mediated antitumor activity, how to deliver CXCL14, what dose to apply, and what combinations with existing therapy may boost antitumor immune responses in cancer patients. Here, we provide updates on the role of CXCL14 in cancer progression and discuss the potential development and application of CXCL14 as an immunotherapeutic agent. Full article
(This article belongs to the Special Issue Immune Responses to Papillomavirus Infections)
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