Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Michele Costanzo
 -- 2494 2023-05-10 16:41:48 |
2 format change
Peter Tang
 Meta information modification 2494 2023-05-11 03:44:22 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Costanzo, M.; De Giglio, M.A.R.; Roviello, G.N. The Oncogenic Potential of SARS-CoV-2. Encyclopedia. Available online: https://encyclopedia.pub/entry/44118 (accessed on 21 December 2024).
Costanzo M, De Giglio MAR, Roviello GN. The Oncogenic Potential of SARS-CoV-2. Encyclopedia. Available at: https://encyclopedia.pub/entry/44118. Accessed December 21, 2024.
Costanzo, Michele, Maria Anna Rachele De Giglio, Giovanni Nicola Roviello. "The Oncogenic Potential of SARS-CoV-2" Encyclopedia, https://encyclopedia.pub/entry/44118 (accessed December 21, 2024).
Costanzo, M., De Giglio, M.A.R., & Roviello, G.N. (2023, May 10). The Oncogenic Potential of SARS-CoV-2. In Encyclopedia. https://encyclopedia.pub/entry/44118
Costanzo, Michele, et al. "The Oncogenic Potential of SARS-CoV-2." Encyclopedia. Web. 10 May, 2023.
The Oncogenic Potential of SARS-CoV-2
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms24097803

Some viruses are known to be associated with the onset of specific cancers. Seven of these microorganisms, recognized as oncogenic viruses or oncoviruses, promote tumorigenesis in humans, converting normal cells into cancer cells through the modulation of central metabolic pathways or the impairment of genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Actually, research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases.

oncoviruses oncogenic virus oncolytic virus SARS-CoV-2 long COVID-19 COVIDomics immunotherapy immune escape metabolic reprogramming coronavirus

1. Introduction

Cancer is still a global threat that seriously affects human life, with a prevalence higher than 10 million deaths yearly [1]. Despite the successful efforts in increasing cancer-free survival rates, many cancer therapies lead to severe undesirable side effects, thus limiting the therapeutic options for cancer treatment [2].
The early diagnosis of cancer and the correct diagnosis, followed by an accurate characterization of the cancer type, are crucial steps in managing cancer patients to increase their survival probability, being the late diagnosis after emergency presentation associated with poor prognosis [3][4][5].
In this context, the already-disposable therapies may be effective only on a restricted number of cancers. Furthermore, the (single or cumulative) events that increase the mutation rate of genes involved in cellular proliferation, DNA repair, or apoptosis correlate with cancer incidence. Among the cancer-inducing events, those triggered by viruses, hence called oncogenic viruses or oncoviruses, are remarkable for being significantly fatal [6][7][8], and their therapy can scarcely improve life expectations in patients. Some virus strains are highly pathogenic per se, and the early diagnosis or the antiviral therapies are often not adequately contemplated. This is often recognized when some oncogenic viruses, coevolving with their asymptomatic human hosts, manifest latent or chronic infections [9]. These viruses may become part of the microbial community of the human host together with other viruses, constituting the so-called human virome [10]. In particular cases, if not pathogenic, they may positively contribute to human health [11]. Virus infections have recognized causal roles in developing several tumors in humans or animals, accounting for around one-fifth of the total cancers [12]. The oncogenic viruses are estimated to be connected with around 15–20% of all human cancers, providing each individual with a ‘risk factor’ of generating tumors caused by virus infection [13][14][15][16].

2. Oncogenic Viruses and Their Mechanisms

Mainly, seven oncoviruses are known to promote the process of tumorigenesis, namely the human papillomavirus (HPV) [17][18][19][20], the hepatitis B and C viruses (HBV, HCV) [21][22][23][24][25], the Epstein-Barr virus (EBV) [26], the human T-cell leukemia virus 1 (HTLV-1) [27][28], the Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8) [29][30], and the Merkel cell polyomavirus (MCPyV) [31][32]. Other potential cases of tumor-inducing viruses may be represented by the human cytomegalovirus (CMV), whose tumorigenic potential is still under investigation [33], as well as the human herpesvirus-6 and the adeno-associated virus-2 [11]. Finally, the human immunodeficiency virus 1 (HIV-1) is indirectly connected with a certain risk of developing cancer upon its mechanisms of immunosuppression [11]. While a comprehensive review based on the oncogenic viruses is out of the scope of this research, here the researchers briefly discuss the seven oncoviruses mainly involved in the carcinogenesis, recapitulating their proposed mechanisms of action, and extracting some elements useful in the context of the SARS-CoV-2 infection.
All the exact biochemical pathways perturbed by virus infections remain undiscovered. The small-size genomes of these viruses range from a few Kb to around 200 Kb, not ensuring an extensive coding ability. As an adaptive consequence, the oncoviruses depend on the host cell proteome to hijack the proliferation of cellular pathways, thus harnessing the whole cell [34]. Therefore, the oncogenesis endorses a multi-step process to be promoted, from the in situ formation of the tumor to the generation of circulating metastatic cells, which depends on the differential regulation of proliferation, apoptosis, and senescence pathways [34]. The seven oncoviruses functionally dysregulate the host cellular pathways involved in cell cycle progression and apoptosis to sustain their propagation. However, despite being jointly characterized by similar mechanisms of pathological infection, the oncogenesis is not indispensable for virus spread from an evolutionary point of view [35].
DNA viruses (HPV, HBV, EBV, HHV-8, MCPyV) encode their virus oncogenes, while RNA viruses (HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation. Oncoviruses may act using different oncogenic mechanisms classified as direct or indirect [36]. In general, direct oncogenesis implicates the insertion of viral oncogenes into the host cell or can be promoted by activating oncogenes already existing in the genome (proto-oncogenes). Indirect viral oncogenesis is promoted by chronic non-specific inflammation occurring over decades of infection, possibly after virus latency inactivity, as for the hepatic cancers induced by HCV. In addition, viruses can integrate their DNA sequences with oncogenic roles. For example, RNA viruses can reverse-transcribe their genome into double-stranded DNA sequences (proviruses) that become successively integrated into the host genome [37]. Specifically, oncogene-containing retroviruses may insert their sequences to enable the transcription of the genes.
On the other hand, oncogene-lacking retroviruses might constitutively activate host proto-oncogenes through proviruses insertion in the nearby proto-oncogene regulatory sequences (insertional mutagenesis); viral promotors take control of the host proto-oncogenes mediating their constitutive activation [37][38] In fact, viral integration into the host genome has been revealed to be a causal mechanism leading to tumor development [39][40], as the additional insertional mutagenesis favors the generation rate of oncogenic mutations, concurring to the genomic instability. Meanly, oncoviruses may straightforwardly trigger the host cell transformation through (i) the integration of a viral oncogene (or only a part of its sequence) into the cellular genome, (ii) the overactivation of human oncogenes, or (iii) the inhibition of tumor suppressors [8]. Thus, the regulation between cell cycle and death signaling is averagely compromised as a target mechanism common to all the oncogenic viruses, despite the fact they express diverse viral products. Moreover, oncoviruses inactivate tumor suppressors and potentiate oncogenes transcription, thus modulating the expression and function of several protein actors and related signaling pathways besides the renowned p53 and pRB, TNF, MAPK, PI3K-AKT-mTOR, WNT/β-catenin, NF-κB and interferon signaling pathways [35][41][42].
Established that cancer development arises from uncontrolled proliferation stimuli and cellular immortality, this complex and multidimensional scenario is accompanied by multiple metabolic dysregulations, immune response escaping, induction of inflammation with the production of reactive oxygen species (ROS), generation of a proper tumor microenvironment, and the genomic instability itself [43][44]. Furthermore, genomic instability and phenotype are further targeted by the generation of genetic and epigenetic changes during the numerous replication cycles, such as DNA methylation and histone modifications, or worsened by co-carcinogenic factors and external stimuli [45][46].

3. The Oncogenic Potential of SARS-CoV-2

The coronavirus disease 19 (COVID-19) caused by SARS-CoV-2 was responsible for huge sanitary and socio-economic difficulties experienced all across the entire world because of the high transmission rates of the virus, its pathogenicity and the lack of effective COVID-19 treatments [47][48][49][50][51] or vaccines [52][53][54] available when it first emerged, and the rapid genetic mutational conversion observed in the last years [55][56][57].
The effects of SARS-CoV-2 infection on cancer patients have been largely investigated for their care and management. It was observed that patients with solid cancer or a hematologic malignancy were more prone to be infected, showing increased morbidity and mortality when compared to the rest of the population [58]. In addition, compared with other tumor types, patients with hematological cancer were more prone to mortality events considering that the dysfunctional immune cells linked to hematopoietic malignancies can significantly shut down the immune defenses of an individual [59].
With such evidence, it becomes clear that the modifications induced by SARS-CoV-2 are substantial for its survival in the host. Additionally, some major signaling pathways have been recognized at the cross-talk between SARS-CoV-2 and cancer cells, frequently stimulating the tumor progression or modifying the response of the tumor to therapy. However, the causal relationship between SARS-CoV-2 and cancer and the effective role of the virus in oncogenesis still represents an open question, considering the observed reactivation of oncogenic viruses following COVID-19 in some cases and the paradoxical response of certain tumors to the immune modulation induced by the infection in others [60].
Similar to oncoviruses, SARS-CoV-2 would be able to promote cancer progression through the alteration of central metabolic pathways in tumor cells and in patients, such as carbon and nitrogen metabolism and nucleic acid metabolism [61][62]. It was found that human biofluids, as well as the infection of Caco-2 (human colon epithelial carcinoma) cells by SARS-CoV-2, affected the proteome negatively regulating the expression of cholesterol-related proteins and positively regulating carbohydrate metabolism-related proteins [37][61][62]. Accordingly, SARS-CoV-2 could excite a metabolic switch in tumor cells to support high-energy production pathways, i.e., glycolysis, for sustaining its replication rate [63][64].
Despite the controversial debate about the oncogenic (or oncolytic) potential of SARS-CoV-2, several genes with a role in oncogenesis have been found regulated upon its infection, such as those corresponding to E2F transcription factors and pRB, thus suggesting a putative mechanism for SARS-CoV-2 in contributing to oncogenesis through the potential inhibition of oncosuppressors [65]. Interactomics studies were pivotal to obtaining such mechanistic insights [66]. Particularly, it was described that the interaction between the endoribonuclease non-structural protein 15 (Nsp15) of SARS-CoV-2 and pRB induces the nuclear export and ubiquitination of pRB for its degradation via proteasome [67]. Furthermore, NIH-3T cells that express the Nsp15 protein did not preserve contact inhibition, displaying an amplified proliferative potential for the induction of cellular transformation [67].
A second potential oncogenic mechanism has been hypothesized for SARS-CoV-2 consisting of the degradation of p53 mediated by the non-structural protein 3 (Nsp3). As previously shown for SARS-CoV-1, the papain-like protease (PLpro) domain of Nsp3 interacts with and stabilizes the E3 ubiquitin ligase RCHY1 [68], thereby promoting the RCHY1-mediated degradation of p53 [69][70]. Furthermore, the Nsp3 protein is highly conserved between SARS-CoV-1 and SARS-CoV-2, showing 76% of sequence similarity. This similarity strongly suggests that SARS-CoV-2 Nsp3 may drive the potential to lower p53 levels promoting its degradation, thus increasing the probability of cellular transformation [6].
The SARS-CoV-2 could provide additional mechanisms to control p53 degradation by hijacking the protein through viral antigens [71][72]. Precisely, the Nsp2 protein of the SARS-CoV-2 interacts with the prohibitins 1 and 2 (PHB1, PHB2) that function as chaperones in the inner mitochondrial membrane for stabilizing the mitochondrial respiratory enzymes and maintaining the mitochondrial integrity. Furthermore, their depletion activates a cascade of cellular responses that prime the leakage of ROS to the nucleus with subsequent oxidative damage, finally impairing the transactivation of p53-dependent genes [72]. Although not demonstrated yet, the ability of the proteins of SARS-CoV-2 to inhibit both p53 and pRB by mediating their degradation suggests that SARS-CoV-2 may have oncogenic potential, triggering internal and external apoptotic pathways within the host cell.
Cancer progression may be potentially favored by SARS-CoV-2-mediated modulation of macro-autophagy/autophagy, proved that diverse coronaviruses can regulate the autophagic machinery [73]. A particular form of autophagy by which the endoplasmic reticulum (ER) is selectively degraded (ER-phagy) seems to be modulated by coronaviruses to drive the formation of double-membrane vesicles (DMVs) that serve as viral replication organelles. Precisely, it was demonstrated that the open reading frame 8 (ORF8) protein of SARS-CoV-2 interacts with p62, the main autophagic cargo receptor, showing that the ORF8/p62 complexes hamper ER-phagy by inhibiting the ER-phagy receptors FAM134B and ATL3 through their aggregation into ORF8/p62 liquid droplets. This mechanism disrupts ER-phagy to promote the formation of new viral DMVs and activation of the ER stress [74]. In addition, it was reported that ORF8 protein directly interacts with major histocompatibility complex class I (MHC-I) molecules, mediating their down-regulation. In particular, SARS-CoV-2-infected cells were significantly less susceptible to cytotoxic T lymphocyte-mediated lysis, being MHC-I molecules selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2 infection could arbitrate immune evasion through down-regulating MHC-I and impairing the antigen presentation system [75]. The role of autophagy in cancer has a miscellaneous facet, with several activities that facilitate cancer cells proliferation and survival, as well as migration and invasion, through recycling metabolites for their growth, regulating their mitochondrial tasks via mitophagy, or controlling the turnover of cell adhesion and the secretion of pro-migratory and inflammatory cytokines, along with adaptation to the microenvironment [76][77]. Modulation of autophagy supports the proliferation of cancerous cells and their survival. Hence, with the ability of SARS-CoV-2 to control to a certain extent the degradation pathways in the cells, cancerogenesis may be promoted by the viral-mediated subversion of autophagy machinery and organelle-specific autophagy.
Further evaluation of a possible correlation between SARS-CoV-2 and cancer arises from the findings of elevated mucin (MUC) levels during COVID-19 infection in patients. MUC glycoproteins are the major macromolecular components of mucus, essential in maintaining the function of districts such as the lung and intestine. In particular, MUC1 is a membrane-bound mucin that shows high expression in the apical membranes of the bronchial epithelium and the gastrointestinal tract. MUC5AC is a secretory mucin expressed mainly in the gastric and tracheobronchial lining. In some cancer-related conditions, glycosylated MUC is abnormally overexpressed by tumors and secreted in the circulation of patients, serving as tumoral biomarkers. Increased MUC1 and MUC5AC mucin protein levels were found in the airway mucus of critically ill COVID-19 patients [78]. In addition, the carbohydrate antigen 72-4 (CA 72-4) marker increased during COVID-19 infection in patients [79]. CA72-4 is a type of cancer-associated polymorphic epithelial MUC, highly expressed in human adenocarcinomas, including gastric, colon, breast, and lung cancer, showing low levels in normal tissues instead. CA72-4 is especially used as an indicator for the tumors of the digestive system [80]. These findings do not provide evidence for direct cancer development but certainly show a possible connection with the onset of tumors in infected patients.
Finally, an alarming situation characterizes COVID-19 patients that do not recover in little time but show sequelae of SARS-CoV-2 infections lasting for months, a condition named as long COVID-19. It has been proposed that long COVID-19 can predispose recovered patients to develop cancer and accelerate cancer progression. This hypothesis has been structured on the mounting evidence of the ability of SARS-CoV-2 to regulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage [81]. Thus, the effects of long COVID-19 on cancer susceptibility need a more profound investigation. In contrast, long-term inhibition of p53 and pRB could be interpreted as an essential risk factor for carcinogenesis.
Long-term relationships between viruses and their hosts are needed for cancer transformation, development, and growth. This is the main reason for the arguments against accurately classifying SARS-CoV-2 as an oncogenic virus. In contrast with classical oncoviruses, and despite the SARS-CoV-2 may exert in vitro oncogenic effects, most infections are resolved in a limited time. Therefore, stating that SARS-CoV-2 is not likely to maintain extremely long-lasting infections opposes its putative role in cancer onset.

References

  1. Zaimy, M.A.; Saffarzadeh, N.; Mohammadi, A.; Pourghadamyari, H.; Izadi, P.; Sarli, A.; Moghaddam, L.K.; Paschepari, S.R.; Azizi, H.; Torkamandi, S.; et al. New methods in the diagnosis of cancer and gene therapy of cancer based on nanoparticles. Cancer Gene Ther. 2017, 24, 233–243.
  2. Boopathi, E.; Thangavel, C. Dark Side of Cancer Therapy: Cancer Treatment-Induced Cardiopulmonary Inflammation, Fibrosis, and Immune Modulation. Int. J. Mol. Sci. 2021, 22, 10126.
  3. Fotouhi, S.; Asadi, S.; Kattan, M.W. A comprehensive data level analysis for cancer diagnosis on imbalanced data. J. Biomed. Inform. 2019, 90, 103089.
  4. Herbert, A.; Abel, G.A.; Winters, S.; McPhail, S.; Elliss-Brookes, L.; Lyratzopoulos, G. Are inequalities in cancer diagnosis through emergency presentation narrowing, widening or remaining unchanged? Longitudinal analysis of English population-based data 2006–2013. J. Epidemiol. Community Health 2019, 73, 3–10.
  5. Raab, S.S.; Grzybicki, D.M. Quality in Cancer Diagnosis. CA Cancer J. Clin. 2010, 60, 139–165.
  6. Stingi, A.; Cirillo, L. SARS-CoV-2 infection and cancer. BioEssays 2021, 43, 2000289.
  7. Arisi, M.; Zane, C.; Caravello, S.; Rovati, C.; Zanca, A.; Venturini, M.; Calzavara-Pinton, P. Sun Exposure and Melanoma, Certainties and Weaknesses of the Present Knowledge. Front. Med. 2018, 5, 235.
  8. Mesri, E.A.; Feitelson, M.A.; Munger, K. Human Viral Oncogenesis: A Cancer Hallmarks Analysis. Cell Host Microbe 2014, 15, 266–282.
  9. Rascovan, N.; Duraisamy, R.; Desnues, C. Metagenomics and the Human Virome in Asymptomatic Individuals. Annu. Rev. Microbiol. 2016, 70, 125–141.
  10. Liang, G.; Bushman, F.D. The human virome: Assembly, composition and host interactions. Nat. Rev. Microbiol. 2021, 19, 514–527.
  11. Schlecht-Louf, G.; Deback, C.; Bachelerie, F. The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy. Cancers 2022, 14, 848.
  12. de Martel, C.; Georges, D.; Bray, F.; Ferlay, J.; Clifford, G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health 2020, 8, e180–e190.
  13. zur Hausen, H.; de Villiers, E.-M. Cancer “Causation” by Infections—Individual Contributions and Synergistic Networks. Semin. Oncol. 2014, 41, 860–875.
  14. Tempera, I.; Lieberman, P.M. Oncogenic Viruses as Entropic Drivers of Cancer Evolution. Front. Virol. 2021, 1, 753366.
  15. Mui, U.; Haley, C.; Tyring, S. Viral Oncology: Molecular Biology and Pathogenesis. J. Clin. Med. 2017, 6, 111.
  16. Cao, J.; Li, D. Searching for human oncoviruses: Histories, challenges, and opportunities. J. Cell. Biochem. 2018, 119, 4897–4906.
  17. Stanley, M. Pathology and epidemiology of HPV infection in females. Gynecol. Oncol. 2010, 117, S5–S10.
  18. Graham, S.V. The human papillomavirus replication cycle, and its links to cancer progression: A comprehensive review. Clin. Sci. 2017, 131, 2201–2221.
  19. Harari, A.; Chen, Z.; Burk, R.D. Human Papillomavirus Genomics: Past, Present and Future. In Human Papillomavirus; Karger: Basel, Switzerland, 2014; pp. 1–18.
  20. Egawa, N.; Egawa, K.; Griffin, H.; Doorbar, J. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia. Viruses 2015, 7, 3863–3890.
  21. Tu, T.; Bühler, S.; Bartenschlager, R. Chronic viral hepatitis and its association with liver cancer. Biol. Chem. 2017, 398, 817–837.
  22. Bandiera, S.; Billie Bian, C.; Hoshida, Y.; Baumert, T.F.; Zeisel, M.B. Chronic hepatitis C virus infection and pathogenesis of hepatocellular carcinoma. Curr. Opin. Virol. 2016, 20, 99–105.
  23. Herrscher, C.; Roingeard, P.; Blanchard, E. Hepatitis B Virus Entry into Cells. Cells 2020, 9, 1486.
  24. Perz, J.F.; Armstrong, G.L.; Farrington, L.A.; Hutin, Y.J.F.; Bell, B.P. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J. Hepatol. 2006, 45, 529–538.
  25. Khatun, M.; Ray, R.B. Mechanisms Underlying Hepatitis C Virus-Associated Hepatic Fibrosis. Cells 2019, 8, 1249.
  26. Naseem, M.; Barzi, A.; Brezden-Masley, C.; Puccini, A.; Berger, M.D.; Tokunaga, R.; Battaglin, F.; Soni, S.; McSkane, M.; Zhang, W.; et al. Outlooks on Epstein-Barr virus associated gastric cancer. Cancer Treat. Rev. 2018, 66, 15–22.
  27. Tagaya, Y.; Gallo, R.C. The Exceptional Oncogenicity of HTLV-1. Front. Microbiol. 2017, 8, 1425.
  28. Brites, C.; Grassi, M.F.; Quaresma, J.A.S.; Ishak, R.; Vallinoto, A.C.R. Pathogenesis of HTLV-1 infection and progression biomarkers: An overview. Braz. J. Infect. Dis. 2021, 25, 101594.
  29. Etta, E.; Alayande, D.; Mavhandu-Ramarumo, L.; Gachara, G.; Bessong, P. HHV-8 Seroprevalence and Genotype Distribution in Africa, 1998–2017: A Systematic Review. Viruses 2018, 10, 458.
  30. Nicholas, J. Human Herpesvirus 8-Encoded Proteins with Potential Roles in Virus-Associated Neoplasia. Front. Biosci. 2007, 12, 265–281.
  31. Pietropaolo, V.; Prezioso, C.; Moens, U. Merkel Cell Polyomavirus and Merkel Cell Carcinoma. Cancers 2020, 12, 1774.
  32. Krump, N.A.; You, J. From Merkel Cell Polyomavirus Infection to Merkel Cell Carcinoma Oncogenesis. Front. Microbiol. 2021, 12, 739695.
  33. De Groof, T.W.M.; Elder, E.G.; Siderius, M.; Heukers, R.; Sinclair, J.H.; Smit, M.J.; Schulte, G. Viral G Protein–Coupled Receptors: Attractive Targets for Herpesvirus-Associated Diseases. Pharmacol. Rev. 2021, 73, 828–846.
  34. Weitzman, M.D.; Fradet-Turcotte, A. Virus DNA Replication and the Host DNA Damage Response. Annu. Rev. Virol. 2018, 5, 141–164.
  35. Krump, N.A.; You, J. Molecular mechanisms of viral oncogenesis in humans. Nat. Rev. Microbiol. 2018, 16, 684–698.
  36. Morales-Sánchez, A.; Fuentes-Pananá, E.M. Human viruses and cancer. Viruses 2014, 6, 4047–4079.
  37. Li, Y.-S.; Ren, H.-C.; Cao, J.-H. Correlation of SARS-CoV-2 to cancer: Carcinogenic or anticancer? (Review). Int. J. Oncol. 2022, 60, 42.
  38. Adoue, V.; Joffre, O. Les rétrovirus endogènes. Med. Sci. 2020, 36, 253–260.
  39. Tang, K.-W.; Larsson, E. Tumour virology in the era of high-throughput genomics. Philos. Trans. R. Soc. B Biol. Sci. 2017, 372, 20160265.
  40. Jiang, Z.; Jhunjhunwala, S.; Liu, J.; Haverty, P.M.; Kennemer, M.I.; Guan, Y.; Lee, W.; Carnevali, P.; Stinson, J.; Johnson, S.; et al. The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients. Genome Res. 2012, 22, 593–601.
  41. Elgui de Oliveira, D. DNA viruses in human cancer: An integrated overview on fundamental mechanisms of viral carcinogenesis. Cancer Lett. 2007, 247, 182–196.
  42. Buchkovich, N.J.; Yu, Y.; Zampieri, C.A.; Alwine, J.C. The TORrid affairs of viruses: Effects of mammalian DNA viruses on the PI3K–Akt–mTOR signalling pathway. Nat. Rev. Microbiol. 2008, 6, 266–275.
  43. Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell 2011, 144, 646–674.
  44. Gaglia, M.M.; Munger, K. More than just oncogenes: Mechanisms of tumorigenesis by human viruses. Curr. Opin. Virol. 2018, 32, 48–59.
  45. McLaughlin-Drubin, M.E.; Crum, C.P.; Münger, K. Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming. Proc. Natl. Acad. Sci. USA 2011, 108, 2130–2135.
  46. Burgers, W.A.; Blanchon, L.; Pradhan, S.; Launoit, Y.d.; Kouzarides, T.; Fuks, F. Viral oncoproteins target the DNA methyltransferases. Oncogene 2006, 26, 1650–1655.
  47. Costanzo, M.; De Giglio, M.A.; Roviello, G.N. SARS-CoV-2: Recent reports on antiviral therapies based on lopinavir/ritonavir, darunavir/umifenovir, hydroxychloroquine, remdesivir, favipiravir and other drugs for the treatment of the new coronavirus. Curr. Med. Chem. 2020, 27, 4536–4541.
  48. Yousefi, H.; Mashouri, L.; Okpechi, S.C.; Alahari, N.; Alahari, S.K. Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action. Biochem. Pharmacol. 2021, 183, 114296.
  49. Borbone, N.; Piccialli, I.; Falanga, A.P.; Piccialli, V.; Roviello, G.N.; Oliviero, G. Nucleic Acids as Biotools at the Interface between Chemistry and Nanomedicine in the COVID-19 Era. Int. J. Mol. Sci. 2022, 23, 4359.
  50. Ricci, A.; Roviello, G.N. Exploring the Protective Effect of Food Drugs against Viral Diseases: Interaction of Functional Food Ingredients and SARS-CoV-2, Influenza Virus, and HSV. Life 2023, 13, 402.
  51. Roviello, V.; Roviello, G.N. Less COVID-19 deaths in southern and insular Italy explained by forest bathing, Mediterranean environment, and antiviral plant volatile organic compounds. Environ. Chem. Lett. 2022, 20, 7–17.
  52. Costanzo, M.; De Giglio, M.A.; Roviello, G.N. Anti-coronavirus vaccines: Past investigations on SARS-CoV-1 and MERS-CoV, the approved vaccines from BioNTech/Pfizer, Moderna, Oxford/AstraZeneca and others under Development Against SARSCoV-2 Infection. Curr. Med. Chem. 2022, 29, 4–18.
  53. Damasceno, D.H.; Amaral, A.A.; Silva, C.A.; Simões e Silva, A.C. The impact of vaccination worldwide on SARS-CoV-2 infection: A review on vaccine mechanisms, results of clinical trials, vaccinal coverage and interactions with novel variants. Curr. Med. Chem. 2022, 29, 2673–2690.
  54. Costanzo, V.; Roviello, G.N. The Potential Role of Vaccines in Preventing Antimicrobial Resistance (AMR): An Update and Future Perspectives. Vaccines 2023, 11, 333.
  55. Cosar, B.; Karagulleoglu, Z.Y.; Unal, S.; Ince, A.T.; Uncuoglu, D.B.; Tuncer, G.; Kilinc, B.R.; Ozkan, Y.E.; Ozkoc, H.C.; Demir, I.N. SARS-CoV-2 mutations and their viral variants. Cytokine Growth Factor Rev. 2022, 63, 10–22.
  56. Magazine, N.; Zhang, T.; Wu, Y.; McGee, M.C.; Veggiani, G.; Huang, W. Mutations and evolution of the SARS-CoV-2 spike protein. Viruses 2022, 14, 640.
  57. Chen, J.; Wang, R.; Wang, M.; Wei, G.-W. Mutations strengthened SARS-CoV-2 infectivity. J. Mol. Biol. 2020, 432, 5212–5226.
  58. Raymond, E.; Thieblemont, C.; Alran, S.; Faivre, S. Impact of the COVID-19 Outbreak on the Management of Patients with Cancer. Target. Oncol. 2020, 15, 249–259.
  59. Dai, M.; Liu, D.; Liu, M.; Zhou, F.; Li, G.; Chen, Z.; Zhang, Z.; You, H.; Wu, M.; Zheng, Q.; et al. Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak. Cancer Discov. 2020, 10, 783–791.
  60. Goubran, H.; Stakiw, J.; Seghatchian, J.; Ragab, G.; Burnouf, T. SARS-CoV-2 and cancer: The intriguing and informative cross-talk. Transfus. Apher. Sci. 2022, 61, 103488.
  61. Costanzo, M.; Caterino, M.; Fedele, R.; Cevenini, A.; Pontillo, M.; Barra, L.; Ruoppolo, M. COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19. Int. J. Mol. Sci. 2022, 23, 2414.
  62. Kim, J.-M.; Kim, H.M.; Lee, E.J.; Jo, H.J.; Yoon, Y.; Lee, N.-J.; Son, J.; Lee, Y.-J.; Kim, M.S.; Lee, Y.-P.; et al. Detection and Isolation of SARS-CoV-2 in Serum, Urine, and Stool Specimens of COVID-19 Patients from the Republic of Korea. Osong Public Health Res. Perspect. 2020, 11, 112–117.
  63. Icard, P.; Lincet, H.; Wu, Z.; Coquerel, A.; Forgez, P.; Alifano, M.; Fournel, L. The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response. Biochimie 2021, 180, 169–177.
  64. Codo, A.C.; Davanzo, G.G.; Monteiro, L.d.B.; de Souza, G.F.; Muraro, S.P.; Virgilio-da-Silva, J.V.; Prodonoff, J.S.; Carregari, V.C.; de Biagi Junior, C.A.O.; Crunfli, F.; et al. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis. Cell Metab. 2020, 32, 498–499.
  65. Policard, M.; Jain, S.; Rego, S.; Dakshanamurthy, S. Immune characterization and profiles of SARS-CoV-2 infected patients reveals potential host therapeutic targets and SARS-CoV-2 oncogenesis mechanism. Virus Res. 2021, 301, 198464.
  66. Santorelli, L.; Caterino, M.; Costanzo, M. Dynamic Interactomics by Cross-Linking Mass Spectrometry: Mapping the Daily Cell Life in Postgenomic Era. OMICS J. Integr. Biol. 2022, 26, 633–649.
  67. Bhardwaj, K.; Liu, P.; Leibowitz, J.L.; Kao, C.C. The Coronavirus Endoribonuclease Nsp15 Interacts with Retinoblastoma Tumor Suppressor Protein. J. Virol. 2012, 86, 4294–4304.
  68. Ma-Lauer, Y.; Carbajo-Lozoya, J.; Hein, M.Y.; Müller, M.A.; Deng, W.; Lei, J.; Meyer, B.; Kusov, Y.; von Brunn, B.; Bairad, D.R.; et al. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1. Proc. Natl. Acad. Sci. USA 2016, 113, E5192–E5201.
  69. Sheng, Y.; Laister, R.C.; Lemak, A.; Wu, B.; Tai, E.; Duan, S.; Lukin, J.; Sunnerhagen, M.; Srisailam, S.; Karra, M.; et al. Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat. Struct. Mol. Biol. 2008, 15, 1334–1342.
  70. Leng, R.P.; Lin, Y.; Ma, W.; Wu, H.; Lemmers, B.; Chung, S.; Parant, J.M.; Lozano, G.; Hakem, R.; Benchimol, S. Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation. Cell 2003, 112, 779–791.
  71. Cardozo, C.M.; Hainaut, P. Viral strategies for circumventing p53: The case of severe acute respiratory syndrome coronavirus. Curr. Opin. Oncol. 2021, 33, 149–158.
  72. Gómez-Carballa, A.; Martinón-Torres, F.; Salas, A. Is SARS-CoV-2 an oncogenic virus? J. Infect. 2022, 85, 573–607.
  73. Sun, Q.; Li, X.; Kuang, E. Subversion of autophagy machinery and organelle-specific autophagy by SARS-CoV-2 and coronaviruses. Autophagy 2023, 19, 1055–1069.
  74. Tan, X.; Cai, K.; Li, J.; Yuan, Z.; Chen, R.; Xiao, H.; Xu, C.; Hu, B.; Qin, Y.; Ding, B. Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication. Cell Rep. 2023, 42, 112286.
  75. Zhang, Y.; Chen, Y.; Li, Y.; Huang, F.; Luo, B.; Yuan, Y.; Xia, B.; Ma, X.; Yang, T.; Yu, F.; et al. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-I. Proc. Natl. Acad. Sci. USA 2021, 118, e2024202118.
  76. Maiti, A.; Hait, N.C. Autophagy-mediated tumor cell survival and progression of breast cancer metastasis to the brain. J. Cancer 2021, 12, 954–964.
  77. Smith, A.G.; Macleod, K.F. Autophagy, cancer stem cells and drug resistance. J. Pathol. 2019, 247, 708–718.
  78. Lu, W.; Liu, X.; Wang, T.; Liu, F.; Zhu, A.; Lin, Y.; Luo, J.; Ye, F.; He, J.; Zhao, J.; et al. Elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID-19 patients. J. Med. Virol. 2021, 93, 582–584.
  79. Knack, R.; Hanada, T.Z.B.; Knack, R.S.; Dana, S.; Afonso, G.L.; Omena, T.; Mayr, K.; Knack, R.S. SARS-CoV-2, a possible new oncovirus? Qeios, 2023; preprint.
  80. Xu, Y.; Zhang, P.; Zhang, K.; Huang, C. The application of CA72-4 in the diagnosis, prognosis, and treatment of gastric cancer. Biochim. Biophys. Acta-Rev. Cancer 2021, 1876, 188634.
  81. Saini, G.; Aneja, R. Cancer as a prospective sequela of long COVID-19. BioEssays 2021, 43, e2000331.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Michele Costanzo
,
Maria Anna Rachele De Giglio
,
Giovanni Nicola Roviello
View Times: 2.5K
Entry Collection: COVID-19
Revisions: 2 times (View History)
Update Date: 11 May 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback