Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that have become fixed in the human genome. While HERV genes are typically silenced in healthy somatic cells, there are numerous reports of HERV transcription and translation across a wide spectrum of cancers, while T and B cell responses against HERV proteins have been detected in cancer patients. This review systematically categorizes the published evidence on the expression of and adaptive immune response against specific HERVs in distinct cancer types. A systematic literature search was performed using Medical Search Headings (MeSH) in the PubMed/Medline database. Papers were included if they described the translational activity of HERVs. We present multiple tables that pair the protein expression of specific HERVs and cancer types with information on the quality of the evidence. We find that HERV-K is the most investigated HERV. HERV-W (syncytin-1) is the second-most investigated, while other HERVs have received less attention. From a therapeutic perspective, HERV-K and HERV-E are the only HERVs with experimental demonstration of effective targeted therapies, but unspecific approaches using antiviral and demethylating agents in combination with chemo- and immunotherapies have also been investigated.

Immunotherapy has been shown to be highly effective in some types of cancer caused by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to correct for inappropriate gene products that cause/may cause diseases. Both these types of therapy have been used as alternative ways to avoid cancers caused by oncoviruses. In this review, we summarize recent studies on immunotherapy and gene therapy including the topics of oncolytic immunotherapy, immune checkpoint inhibitors, gene replacement, antisense oligonucleotides, RNA interference, clustered regularly interspaced short palindromic repeats Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene editing, transcription activator-like effector nucleases (TALENs) and custom treatment for Epstein-Barr virus, human T-lymphotropic virus 1, hepatitis B virus, human papillomavirus, hepatitis C virus, herpesvirus associated with Kaposi\'s sarcoma, Merkel cell polyomavirus, and cytomegalovirus.

Koala retrovirus (KoRV) is a major threat to koala health and conservation. It also represents a series of challenges across the fields of virology, immunology, and epidemiology that are of great potential interest to any researcher in the field of retroviral diseases. KoRV is a gammaretrovirus that is present in both endogenous and exogenous forms in koala populations, with a still-active endogenization process. KoRV may induce immunosuppression and neoplastic conditions such as lymphoma and leukemia and play a role in chlamydiosis and other diseases in koalas. KoRV transmission modes, pathogenesis, and host immune response still remain unclear, and a clear understanding of these areas is critical for devising effective preventative and therapeutic strategies. Research on KoRV is clearly critical for koala conservation. In this review, we provide an overview of the current understanding and future challenges related to KoRV epidemiology, transmission mode, pathogenesis, and host immune response and discuss prospects for therapeutic and preventive vaccines.

BACKGROUND: Gastric cancer is one of the infection associated malignancies. In addition to Helicobacter pylori and Epstein-Barr virus (EBV), other oncoviruses might play potential roles in the development of gastric cancer. Associations of oncoviruses other than EBV with gastric cancer risk are aimed to be comprehensively reviewed and assessed in this systematic review and meta-analysis, to identify any potentially causative oncovirus. It might be informative to identify or deny certain oncoviruses which are candidates of risk factor for gastric cancer. To our knowledge, there is no comprehensive review on oncoviruses other than EBV associated with gastric cancer risk. Positive findings might be helpful to suggest further mechanism investigation and high-risk subpopulation recommendation.
METHODS: PubMed database will be searched up to Dec 31, 2018. The studies, compared the positivity of any oncovirus other than EBV between cases with histologically proven gastric cancer and healthy or nonmalignant controls, are eligible. The detection of oncovirus either in tissue or blood is acceptable. Selection, quality assessment (Newcastle-Ottawa Scale), and data extraction of eligible studies will be performed by 2 independent reviewers. Pooled prevalence of any oncovirus will be combined by meta-analysis for rate. Pooled odds ratio between gastric cancer cases and controls will be estimated by meta-analysis. Heterogeneity and publication bias will be tested. In sensitivity analysis, the leave-one-out method and exclusion of low power studies will be applied where applicable.
RESULTS: This review was not submitted for any ethical approval due to the literature-based nature. The results will be published in a journal and presented at conferences for academic purposes.Registration number was CRD42015029703 in the PROSPERO International Prospective Register of Systematic Reviews.
CONCLUSIONS: To our knowledge, there is no comprehensive review on oncoviruses other than EBV associated with gastric cancer risk. Positive findings might be helpful to suggest further mechanism investigation and high-risk subpopulation recommendation.

The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered \"junk DNA\" and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.

Koala retrovirus (KoRV) is a gammaretrovirus that has been identified in both captive and free-ranging koalas ( Phascolarctos cinereus ) with variable geographic distribution in Australia. KoRV is capable of both exogenous and endogenous transmission, which provides an interesting research platform for scientists to study active retrovirus endogenization into a host genome and offers veterinary scientists an opportunity to examine the clinical consequences of KoRV infection in koalas. Causation between KoRV and frequently recognized clinical conditions associated with immune suppression and neoplasia in koalas has not been definitively established, however research continues to evaluate a potential association. Three KoRV variants, KoRV-A, KoRV-B, and KoRV-J, have been the most thoroughly described and preliminary evidence suggests KoRV variability may be fundamental in host pathogenicity. In addition to reviewing what is currently known about KoRV, this article discusses treatment, management, and future research directions.

Specific pathogen free (SPF) macaques provide valuable animal models for biomedical research. In 1989, the National Center for Research Resources [now Office of Research Infrastructure Programs (ORIP)] of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilitiy management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making.

Xenotransplantation of porcine organs, tissues, and cells inherits a risk for xenozoonotic infections. Viable tissues and cells intended for transplantation have to be considered as potentially contaminated non-sterile products. The demands on microbial testing, based on the regulatory requirements, are often challenging due to a restricted shelf life or the complexity of the product itself. In Europe, the regulatory framework for xenogeneic cell therapy is based on the advanced therapy medicinal products (ATMP) regulation (2007), the EMA CHMP Guideline on xenogeneic cell-based medicinal products (2009), as well as the WHO and Council of Europe recommendations. In the USA, FDA guidance for industry (2003) regulates the use of xenotransplants. To comply with the regulations, validated test methods need to be established that reveal the microbial status of a transplant within its given shelf life, complemented by strictly defined action alert limits and supported by breeding in specific pathogen-free (SPF) facilities. In this review, we focus on assays for the detection of the porcine endogenous retroviruses PERV-A/-B/-C, which exhibit highly polymorphic proviral loci in pig genomes. PERVs are transmitted vertically and cannot be completely eliminated by breeding or gene knock out technology. PERVs entail a public health concern that will persist even if no evidence of PERV infection of xenotransplant recipients in vivo has been revealed yet. Nevertheless, infectious risks must be minimized by full assessment of pigs as donors by combining different molecular screening assays for sensitive and specific detection as well as a functional analysis of the infectivity of PERV including an adequate monitoring of recipients.

Thirteen proliferative diseases in fish have been associated in the literature with 1 or more retroviruses. Typically, these occur as seasonal epizootics affecting farmed and wild fish, and most lesions resolve spontaneously. Spontaneous resolution and lifelong resistance to reinfection are 2 features of some piscine retrovirus-induced tumors that have stimulated research interest in this field. The purpose of this review is to present the reader with the epidemiological and morphological features of proliferative diseases in fish that have been associated with retroviruses by 1 or more of the following methods: detection of C-type retrovirus-like particles or reverse transcriptase activity in tumor tissues; successful tumor transmission trials using well-characterized, tumor-derived, cell-free inocula; or molecular characterization of the virus from spontaneous and experimentally induced tumors. Two of the diseases included in this review, European smelt spawning papillomatosis and bicolor damselfish neurofibromatosis, at one time were attributed to a retroviral etiology, but both are now believed to involve additional viral agents based on more recent investigations. We include the latter 2 entities to update the reader about these developments.

This review is an updated summary of nearly 30 years of SRV history and provides new and critical findings of original research accomplished in the last 5 years including, but not limited to, the pathogenetic mechanisms underlying the origin of hematopoietic abnormalities observed in infected hosts and proposed new SRV serotypes. Despite major advances in the understanding and control of SRV disease, much more remains to be learned and SRV continues to be an exciting and attractive primate model for comparative studies of the mechanisms of retroviral immunosuppression.