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Current Opinion in Virology Aug 2019Although bacterial dysbiosis has been previously associated with carcinogenesis and HIV infection, the impact of the virome and these disease states has been less well... (Review)
Review
Although bacterial dysbiosis has been previously associated with carcinogenesis and HIV infection, the impact of the virome and these disease states has been less well studied. In this review, we will summarize what is known about the interplay between both the bacterial and the viral components of the microbiome on cancer and HIV pathogenesis. Bacterial dysbiosis has been associated with carcinogenesis such as colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer, breast cancer, and gastric cancer. The dysbiotic pathogenesis may be species-based or community-based and can have varying mechanisms of carcinogenesis. The human virome was also associated with certain cancers. Viruses, such as cytomegalovirus (CMV), Human herpesvirus 8 (HHV-8), human papilloma virus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV), all had associations with cancers. It was also reported that an altered bacteriophage community may lead to carcinogenesis by allowing opportunistic, oncogenic bacteria to proliferate in a gastrointestinal biofilm. This mechanism shows the importance of analyzing the bacteriome and the virome concurrently as their interactions can provide insight into new mechanisms in the pathogenesis of not only cancer, but other diseases as well. The enteric bacteriome was shown to be distinctly altered in immunocompromised HIV-infected individuals, and highly active antiretroviral therapy (HAART) was shown to at least partially reverse the alterations that HIV causes in the bacteriome. Studies have shown that the progression to HIV is associated with changes in the plasma concentration of commensal viruses. HIV also acts synergistically with multiple other viruses, such as HPV, EBV, varicella zoster virus (VZV), and HHV-8. Although it has been shown that HIV infection leads to enteric virome expansion in humans, most of the research on HIV's effect on the virome was conducted in non-human primates, and there is a lack of research on the effect of HAART on the virome. Virome-wide analysis is necessary for identifying novel viral etiologies. There is currently a wealth of information on the bacteriome and its associations with cancer and HIV, but more research should be conducted on the virome's associations and reaction to HAART as well as the bacteriome-virome interactions that may play a major role in pathogenesis and recovery.
Topics: Antiretroviral Therapy, Highly Active; Bacteria; Bacteriophages; Carcinoma, Hepatocellular; Cytomegalovirus; DNA, Viral; Dysbiosis; HIV Infections; Hepatitis B virus; Herpesvirus 4, Human; Herpesvirus 8, Human; Host Microbial Interactions; Humans; Liver Neoplasms; Microbial Interactions; Microbiota; Neoplasms; Virus Diseases; Viruses
PubMed: 31177014
DOI: 10.1016/j.coviro.2019.05.007 -
Tumour Virus Research Dec 2022Human tumor viruses cause various human cancers that account for at least 15% of the global cancer burden. Among the currently identified human tumor viruses, two are... (Review)
Review
Human tumor viruses cause various human cancers that account for at least 15% of the global cancer burden. Among the currently identified human tumor viruses, two are small DNA tumor viruses: human papillomaviruses (HPVs) and Merkel cell polyomavirus (MCPyV). The study of small DNA tumor viruses (adenoviruses, polyomaviruses, and papillomaviruses) has facilitated several significant biological discoveries and established some of the first animal models of virus-associated cancers. The development and use of preclinical in vivo models to study HPVs and MCPyV and their role in human cancer is the focus of this review. Important considerations in the design of animal models of small DNA tumor virus infection and disease, including host range, cell tropism, choice of virus isolates, and the ability to recapitulate human disease, are presented. The types of infection-based and transgenic model strategies that are used to study HPVs and MCPyV, including their strengths and limitations, are also discussed. An overview of the current models that exist to study HPV and MCPyV infection and neoplastic disease are highlighted. These comparative models provide valuable platforms to study various aspects of virus-associated human disease and will continue to expand knowledge of human tumor viruses and their relationship with their hosts.
Topics: Animals; Humans; Merkel cell polyomavirus; Polyomavirus Infections; Tumor Virus Infections; Neoplasms; Polyomavirus; Oncogenic Viruses
PubMed: 35636683
DOI: 10.1016/j.tvr.2022.200239 -
Cancer Informatics 2023This review discusses the possible involvement of infections-associated cancers in humans, with virus infections contributing 15% to 20% of total cancer cases in humans.... (Review)
Review
This review discusses the possible involvement of infections-associated cancers in humans, with virus infections contributing 15% to 20% of total cancer cases in humans. DNA virus encoded proteins interact with host cellular signaling pathways and control proliferation, cell death and genomic integrity viral oncoproteins are known to bind cellular Deubiquitinates (DUBs) such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, and A-20 to improve their intracellular stability and cellular signaling pathways and finally transformation. Human papillomaviruses (cervical carcinoma, oral cancer and laryngeal cancer); human polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B (hepatocellular carcinoma (HCC)) cause up to 20% of malignancies around the world.
PubMed: 37363356
DOI: 10.1177/11769351231154186 -
Journal of Medical Virology Jan 2023Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are two persistent oncogenic γ-herpesviruses with an exclusive tropism for humans. They cause... (Review)
Review
Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are two persistent oncogenic γ-herpesviruses with an exclusive tropism for humans. They cause cancers of lymphocyte, epithelial and endothelial cell origin, such as Burkitt's and Hodgkin's lymphoma, primary effusion lymphoma, nasopharyngeal carcinoma, and Kaposi sarcoma. Mutations in immune-related genes but also adverse events during immune checkpoint inhibition in cancer patients have revealed molecular requirements for immune control of EBV and KSHV. These include costimulatory and coinhibitory receptors on T cells that are currently explored or already therapeutically targeted in tumor patients. This review discusses these co-receptors and their influence on EBV- and KSHV-associated diseases. The respective studies reveal surprising specificities of some of these receptors for immunity to these tumor viruses, benefits of their blockade for some but not other virus-associated diseases, and that EBV- and KSHV-specific immune control should be monitored during immune checkpoint inhibition to prevent adverse events that might be associated with their reactivation during treatment.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Immune Checkpoint Inhibitors; T-Lymphocytes; Sarcoma, Kaposi; Herpesviridae Infections; Herpesvirus 8, Human; Neoplasms
PubMed: 35524342
DOI: 10.1002/jmv.27840 -
Frontiers in Cellular and Infection... 2022The commensal microbiome refers to a large spectrum of microorganisms which mainly consists of viruses and bacteria, as well as some other components such as protozoa... (Review)
Review
The commensal microbiome refers to a large spectrum of microorganisms which mainly consists of viruses and bacteria, as well as some other components such as protozoa and fungi. Epstein-Barr virus (EBV) is considered as a common component of the human commensal microbiome due to its spread worldwide in about 95% of the adult population. As the first oncogenic virus recognized in human, numerous studies have reported the involvement of other components of the commensal microbiome in the increasing incidence of EBV-driven cancers. Additionally, recent advances have also defined the involvement of host-microbiota interactions in the regulation of the host immune system in EBV-driven cancers as well as other circumstances. The regulation of the host immune system by the commensal microbiome coinfects with EBV could be the implications for how we understand the persistence and reactivation of EBV, as well as the progression of EBV-associated cancers, since majority of the EBV persist as asymptomatic carrier. In this review, we attempt to summarize the possible mechanisms for EBV latency, reactivation, and EBV-driven tumorigenesis, as well as casting light on the role of other components of the microbiome in EBV infection and reactivation. Besides, whether novel microbiome targeting strategies could be applied for curing of EBV-driven cancer is discussed as well.
Topics: Adult; Carcinogenesis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Host Microbial Interactions; Humans; Microbiota
PubMed: 35281433
DOI: 10.3389/fcimb.2022.852066 -
Seminars in Hematology Oct 2022Lymphomas are among the most common cancers in people with HIV (PWH). The lymphoma subtypes and pathogenesis of lymphoma in PWH are different from the immunocompetent...
Lymphomas are among the most common cancers in people with HIV (PWH). The lymphoma subtypes and pathogenesis of lymphoma in PWH are different from the immunocompetent population. It is well-known that HIV causes severe CD4 T cell lymphopenia in the absence of antiretroviral therapy (ART); however, the risk of developing certain subtypes of lymphoma remains elevated even in people receiving ART with preserved CD4 T cells. HIV contributes to lymphomagenesis and causes decreased immune surveillance via T cell depletion and dysregulation, B cell dysregulation, and the potential contribution of HIV-encoded proteins. The oncogenic gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8), are the causative agents in the majority of HIV-associated lymphomas. HIV-associated T cell depletion and dysregulation allows EBV and KSHV to proliferate in infected B cells. Specific EBV- and KSHV-encoded proteins participate in B cell activation, and proliferation leading to B cell transformation. Understanding the distinct pathogenesis of HIV-associated lymphomas affords opportunities to develop therapies that specifically target these unique aspects and improve lymphoma outcomes in PWH. Agents being studied that target the specific roles of HIV, EBV, and KSHV in lymphomagenesis include immunotherapies, targeted agents, and cellular therapies.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Lymphoma; Immunotherapy
PubMed: 36805886
DOI: 10.1053/j.seminhematol.2022.11.002 -
Clinical Microbiology Reviews Apr 2022Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult... (Review)
Review
Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.
Topics: Adult; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic; Public Health
PubMed: 35195446
DOI: 10.1128/cmr.00078-21 -
Veterinary Microbiology Feb 2024The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal... (Review)
Review
The family Papillomaviridae includes a plethora of viral species infecting virtually all vertebrates excluding amphibians, with astonishing impact on human and animal health. Although more than 250 species have been described in humans, the total number of papillomaviruses (PVs) discovered in animals does not reach up to this number. In animals, PV infections are mostly asymptomatic or can cause variable clinical conditions ranging from self-limiting papillomas and other cutaneous and mucosal benign lesions to cancer. Most of animal PV types have been discovered in cattle, dogs, horses, and cats with other farm host species remaining overlooked. In particular, the number of PV types so far identified in sheep is limited. This paper comprehensively reviews ovine PVs features, including viral taxonomy and evolution; genome organization; viral tropism and pathogenesis; macroscopical features and histopathological patterns, as well as available diagnostics tools. Data are critically presented and discussed in terms of impact on veterinary and public health. The development of future dedicated research is also discussed.
Topics: Animals; Deltapapillomavirus; Papilloma; Papillomaviridae; Papillomavirus Infections; Sheep; Sheep Diseases; Virulence
PubMed: 38160507
DOI: 10.1016/j.vetmic.2023.109955 -
PLoS Medicine Oct 2023Cervical screening programs use testing for human papillomavirus (HPV) genotypes. Different HPV types differ greatly in prevalence and oncogenicity. We estimated the...
BACKGROUND
Cervical screening programs use testing for human papillomavirus (HPV) genotypes. Different HPV types differ greatly in prevalence and oncogenicity. We estimated the impact of cervical screening and follow-up for each HPV type.
METHODS AND FINDINGS
For each type of HPV, we calculated the number of women needed to screen (NNS) and number of women needing follow-up (NNF) to detect or prevent one cervical cancer case, using the following individual level input data (i) screening and cancer data for all women aged 25 to 80 years, resident in Sweden during 2004 to 2011 (N = 3,568,938); (ii) HPV type-specific prevalences and screening histories among women with cervical cancer in Sweden in 2002 to 2011(N = 4,254); (iii) HPV 16/18/other HPV prevalences in the population-based HPV screening program (N = 656,607); and (iv) exact HPV genotyping in a population-based cohort (n = 12,527). Historical screening attendance was associated with a 72% reduction of cervical cancer incidence caused by HPV16 (71.6%, 95% confidence interval (CI) [69.1%, 73.9%]) and a 54% reduction of cancer caused by HPV18 (53.8%, 95% CI [40.6%, 63.1%]). One case of HPV16-caused cervical cancer could be prevented for every 5,527 women attending screening (number needed to screen, NNS). Prevention of one case of HPV16-caused cervical cancer required follow-up of 147 HPV16-positive women (number needed to follow-up, NNF). The NNS and NNF were up to 40 to 500 times higher for HPV types commonly screened for with lower oncogenic potential (HPV35,39,51,56,59,66,68). For women below 30 years of age, NNS and NNF for HPV16 were 4,747 and 289, respectively, but >220,000 and >16,000 for HPV35,39,51,56,59,66,68. All estimates were either age-standarized or age-stratified. The primary limitation of our study is that NNS is dependent on the HPV prevalence that can differ between populations and over time. However, it can readily be recalculated in other settings and monitored when HPV type-specific prevalence changes. Other limitations include that in some age groups, there was little data and extrapolations had to be made. Finally, there were very few cervical cancer cases associated with certain HPV types in young age group.
CONCLUSIONS
In this study, we observed that the impact of cervical cancer screening varies depending on the HPV type screened for. Estimating and monitoring the impact of screening by HPV type can facilitate the design of effective and efficient HPV-based cervical screening programs.
TRIAL REGISTRATION
ClinicalTrials.gov with numbers NCT00479375, NCT01511328.
Topics: Female; Humans; Uterine Cervical Neoplasms; Early Detection of Cancer; Human Papillomavirus Viruses; Human papillomavirus 16; Papillomavirus Infections; Human papillomavirus 18; Papillomaviridae; Genotype
PubMed: 37889928
DOI: 10.1371/journal.pmed.1004304 -
International Journal of Molecular... Nov 2022Epstein-Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90-95% of the population has... (Review)
Review
Epstein-Barr virus (EBV) is one of eight known herpesviruses with the potential to infect humans. Globally, it is estimated that between 90-95% of the population has been infected with EBV. EBV is an oncogenic virus that has been strongly linked to various epithelial malignancies such as nasopharyngeal and gastric cancer. Recent evidence suggests a link between EBV and breast cancer. Additionally, there are other, rarer cancers with weaker evidence linking them to EBV. In this review, we discuss the currently known epithelial malignancies associated with EBV. Additionally, we discuss and establish which treatments and therapies are most recommended for each cancer associated with EBV.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Stomach Neoplasms; Nasopharynx; Neoplasms, Glandular and Epithelial
PubMed: 36430864
DOI: 10.3390/ijms232214389