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Viruses
Special Issues
Chronic Infection by Oncogenic Viruses
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Chronic Infection by Oncogenic Viruses

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 15056

Special Issue Editor

Prof. Dr. Christophe Nicot

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Center for Viral Oncology, Kansas City, KS, USA
Interests: HTLV-1; leukemia; oncogenesis; signal transduction pathways

Special Issue Information

Dear Colleague,

The study of oncogenic viruses has provided many basic insights into cancer, the most important of which is the identification and functional characterization of many oncogenes and tumor suppressor genes. In contrast to acute viruses, chronic viruses establish a persistent lifelong infection of their host. Chronic viral infections can be classified into different categories: Latent infections, characterized by minimal viral production during the initial and late stages. Productive infections, where persistent viral production occurs throughout the entire span, from initial infection to the late stages. Slow infections are marked by a gradual increase in viral production, starting from the incubation period and progressing to the late stages. The distinction among these stages is defined by the regulation of viral propagation and the alteration of viral gene expression patterns.

In this Special Issue, we will focus on the most recent advances in the understanding of the mechanisms of human oncogenic virus replication and pathogenesis. We will also focus on new developments in treatment, antiviral strategies, and vaccine development.

Prof. Dr. Christophe Nicot
Guest Editor

Manuscript Submission Information

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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

  • virus transmission
  • virus replication
  • virus pathogenesis
  • virus latency
  • virus–host interactions
  • antiviral immune responses
  • virus-induced cellular transformation
  • antiviral drugs and vaccines

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Published Papers (6 papers)

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Research

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26 pages, 4812 KiB  
Article
Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
by Linda Saxe Einbond, Jing Zhou, Kunhui Huang, Mario R. Castellanos, Emeka Mbazor, Michael Balick, Hongbao Ma, James A. DeVoti, Stephen Redenti and Hsan-au Wu
Viruses 2025, 17(1), 55; https://doi.org/10.3390/v17010055 - 31 Dec 2024
Viewed by 1010
Abstract
This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. [...] Read more.
This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays. W12 cells, derived from a cervical precancerous lesion, contain either episomal or integrated HPV16 DNA. Several compounds, including digoxin, tanshinone IIA, dihydromethysticin and carrageenan, as well as fractions of turmeric, ginger and pomegranate inhibited the growth of W12 precancer and cervical cancer cells. Curcumin and tanshinone IIA were the most active and relatively nontoxic compounds. RT-PCR analysis showed that tanshinone IIA activated the expression of p53, while repressing the expression of HPV16 E1, E2, E4, E6, and E7 viral transcripts in W12 (type 1 and 2) integrant cells. In addition, curcumin synergized with tanshinone IIA in HeLa cells. Molecular docking studies suggested tanshinone IIA and curcumin bind to the Na+/K+-ATPase ion channel, with curcumin binding with higher affinity. Our findings highlight the potential of these multifaceted phytochemicals to prevent and treat HPV-induced cervical cancer, offering a promising approach for combinatorial therapeutic intervention. Full article
(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)
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21 pages, 3331 KiB  
Article
Characterization of HTLV-1 Infectious Molecular Clone Isolated from Patient with HAM/TSP and Immortalization of Human Primary T-Cell Lines
by Marcia Bellon, Pooja Jain and Christophe Nicot
Viruses 2024, 16(11), 1755; https://doi.org/10.3390/v16111755 - 9 Nov 2024
Viewed by 1235
Abstract
Human T-cell leukemia virus (HTLV-1) is the etiological agent of lymphoproliferative diseases such as adult T-cell leukemia and T-cell lymphoma (ATL) and a neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While several molecular clones of HTLV-1 have been published, all were [...] Read more.
Human T-cell leukemia virus (HTLV-1) is the etiological agent of lymphoproliferative diseases such as adult T-cell leukemia and T-cell lymphoma (ATL) and a neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While several molecular clones of HTLV-1 have been published, all were isolated from samples derived from patients with adult T-cell leukemia. Here, we report the characterization of an HTLV-1 infectious molecular clone isolated from a sample of a patient with HAM/TSP disease. Genetic comparative analyses of the HAM/TSP molecular clone (pBST) revealed unique genetic alterations and specific viral mRNA expression patterns. Interestingly, our clone also harbors characteristics previously published to favor the development of HAM/TSP disease. The molecular clone is capable of infection and immortalization of human primary T cells in vitro. Our studies further demonstrate that the HTLV-1 virus produced from primary T cells transfected with pBST or ACH molecular clones cannot sustain long-term expansion, and cells cease to proliferate after 3–4 months in culture. In contrast, long-term proliferation and immortalization were achieved if the virus was transmitted from dendritic cells to primary T cells, and secondary infection of 729B cells in vitro was demonstrated. In both primary T cells and 729B cells, pBST and ACH were latent, and only hbz viral RNA was detected. This study suggests that HTLV-1 transmission from DC to T cells favors the immortalization of latently infected cells. Full article
(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)
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18 pages, 3984 KiB  
Article
Susceptibility of HPV-18 Cancer Cells to HIV Protease Inhibitors
by Lilian Makgoo, Salerwe Mosebi and Zukile Mbita
Viruses 2024, 16(10), 1622; https://doi.org/10.3390/v16101622 - 17 Oct 2024
Viewed by 1378
Abstract
Cervical cancer cases continue to rise despite all the advanced screening and preventative measures put in place, which include human papillomavirus (HPV) vaccination. These soaring numbers can be attributed to the lack of effective anticancer drugs against cervical cancer; thus, repurposing the human [...] Read more.
Cervical cancer cases continue to rise despite all the advanced screening and preventative measures put in place, which include human papillomavirus (HPV) vaccination. These soaring numbers can be attributed to the lack of effective anticancer drugs against cervical cancer; thus, repurposing the human immunodeficiency virus protease inhibitors is an attractive innovation. Therefore, this work was aimed at evaluating the potential anticancer activities of HIV-PIs against cervical cancer cells. The MTT viability assay was used to evaluate the effect of HIV protease inhibitors on the viability of cervical cancer cells (HeLa) and non-cancerous cells (HEK-293). Further confirmation of the MTT assay was performed by confirming the IC50s of these HIV protease inhibitors on cervical cancer cells and non-cancerous cells using the Muse™ Count and Viability assay. To confirm the mode of death induced by HIV protease inhibitors in the HPV-associated cervical cancer cell line, apoptosis was performed using Annexin V assay. In addition, the Muse™ Cell Cycle assay was used to check whether the HIV protease inhibitors promote or halt cell cycle progression in cervical cancer cells. HIV protease inhibitors did not affect the viability of non-cancerous cells (HEK-293), but they decreased the viability of HeLa cervical cancer cells in a dose-dependent manner. HIV protease inhibitors induced apoptosis in HPV-related cervical cancer cells. Furthermore, they also induced cell cycle arrest, thus halting cell cycle progression. Therefore, the use of HIV drugs, particularly HIV-1 protease inhibitors, as potential cancer therapeutics represents a promising strategy. This is supported by our study demonstrating their anticancer properties, notably in HPV-associated cervical cancer cell line. Full article
(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)
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15 pages, 2244 KiB  
Article
Diagnostic Value of Anti-HTLV-1-Antibody Quantification in Cerebrospinal Fluid for HTLV-1-Associated Myelopathy
by Tomoo Sato, Naoko Yagishita, Natsumi Araya, Makoto Nakashima, Erika Horibe, Katsunori Takahashi, Yasuo Kunitomo, Yukino Nawa, Isao Hamaguchi and Yoshihisa Yamano
Viruses 2024, 16(10), 1581; https://doi.org/10.3390/v16101581 - 8 Oct 2024
Viewed by 1246
Abstract
The diagnostic accuracy of cerebrospinal fluid (CSF) anti-human T-cell leukemia virus type I (HTLV-1) antibody testing for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) remains unclear. Therefore, we measured the anti-HTLV-1 antibody levels in CSF using various test kits, evaluated the stability of CSF antibodies, [...] Read more.
The diagnostic accuracy of cerebrospinal fluid (CSF) anti-human T-cell leukemia virus type I (HTLV-1) antibody testing for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) remains unclear. Therefore, we measured the anti-HTLV-1 antibody levels in CSF using various test kits, evaluated the stability of CSF antibodies, and performed a correlation analysis using the particle agglutination (PA) method, as well as a receiver operating characteristic (ROC) analysis between patients with HAM and carriers. The CSF anti-HTLV-1 antibody levels were influenced by freeze–thaw cycles but remained stable when the CSF was refrigerated at 4 °C for up to 48 h. Measurements from 92 patients (69 patients with HAM and 23 carriers) demonstrated a strong correlation (r > 0.9) with the PA method across all six quantifiable test kits. All six test kits, along with CSF neopterin and CXCL10, exhibited areas under the ROC curve greater than 0.9, indicating a high diagnostic performance for HAM. Among these, five test kits, Lumipulse and Lumipulse Presto HTLV-I/II, HISCL-UD (a kit under development), HTLV-Abbott, and Elecsys HTLV-I/II, established a cutoff with 100% sensitivity and maximum specificity, achieving a sensitivity of 100% and a specificity ranging from 43.5% to 56.5%. This cutoff value, in combination with clinical findings, will aid in the accurate diagnosis of HAM. Full article
(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)
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Review

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26 pages, 2144 KiB  
Review
Monocyte and Macrophage Functions in Oncogenic Viral Infections
by Juliana Echevarria-Lima and Ramona Moles
Viruses 2024, 16(10), 1612; https://doi.org/10.3390/v16101612 - 15 Oct 2024
Viewed by 1808
Abstract
Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent [...] Read more.
Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent 5% of the nucleated cells in normal adult blood. Following differentiation, macrophages are distributed into various tissues and organs to take residence and maintain body homeostasis. Emerging evidence has highlighted the critical role of monocytes/macrophages in oncogenic viral infections, mainly their crucial functions in viral persistence and disease progression. These findings open opportunities to target innate immunity in the context of oncogenic viruses and to explore their potential as immunotherapies. Full article
(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)
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12 pages, 742 KiB  
Review
Human Papillomavirus and Associated Cancers: A Review
by JaNiese E. Jensen, Greta L. Becker, J. Brooks Jackson and Mary B. Rysavy
Viruses 2024, 16(5), 680; https://doi.org/10.3390/v16050680 - 26 Apr 2024
Cited by 24 | Viewed by 6851
Abstract
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of [...] Read more.
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide. Full article
(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)
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