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Viruses Jul 2020Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how... (Review)
Review
Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how to limit infection. Mouse retroviruses that are endemic in their hosts provide an important genetic tool to dissect the different arms of the innate immune system that recognize retroviruses as foreign. Here, we review what is known about the major branches of the innate immune system that respond to mouse retrovirus infection, Toll-like receptors and nucleic acid sensors, and discuss the importance of these responses in activating adaptive immunity and controlling infection.
Topics: Animals; Host Microbial Interactions; Immunity, Innate; Mice; Retroviridae; Retroviridae Infections; Virus Replication
PubMed: 32751803
DOI: 10.3390/v12080836 -
Viruses Oct 2021Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for... (Review)
Review
Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for xenotransplantation, the transplantation of pig cells, tissues, or organ to humans in order to alleviate the shortage of human donor organs. Up to 2021, a huge body of knowledge about PERVs has been accumulated regarding their biology, including replication, recombination, origin, host range, and immunosuppressive properties. Until now, no PERV transmission has been observed in clinical trials transplanting pig islet cells into diabetic humans, in preclinical trials transplanting pig cells and organs into nonhuman primates with remarkable long survival times of the transplant, and in infection experiments with several animal species. Nevertheless, in order to prevent virus transmission to the recipient, numerous strategies have been developed, including selection of PERV-C-free animals, RNA interference, antiviral drugs, vaccination, and genome editing. Furthermore, at present there are no more experimental approaches to evaluate the full risk until we move to the clinic.
Topics: Animals; Endogenous Retroviruses; Gammaretrovirus; Host Specificity; Immunosuppressive Agents; Retroviridae Infections; Swine; Swine Diseases; Transplantation, Heterologous; Zoonoses
PubMed: 34834962
DOI: 10.3390/v13112156 -
Retrovirology Dec 2017Foamy viruses (FV) are ancient complex retroviruses that differ from orthoretroviruses such as human immunodeficiency virus (HIV) and murine leukemia virus (MLV) and... (Review)
Review
BACKGROUND
Foamy viruses (FV) are ancient complex retroviruses that differ from orthoretroviruses such as human immunodeficiency virus (HIV) and murine leukemia virus (MLV) and comprise a distinct subfamily of retroviruses, the Spumaretrovirinae. FV are ubiquitous in their natural hosts, which include cows, cats, and nonhuman primates (NHP). FV are transmitted mainly through saliva and appear nonpathogenic by themselves, but they may increase morbidity of other pathogens in coinfections.
CONCLUSIONS
This review summarizes and discusses what is known about FV infection of natural hosts. It also emphasizes what is known about FV zoonotic infections A large number of studies have revealed that the FV of NHP, simian foamy viruses (SFV), are transmitted to humans who interact with infected NHP. SFV from a variety of NHP establish persistent infection in humans, while bovine foamy virus and feline foamy virus rarely or never do. The possibility of FV recombination and mutation leading to pathogenesis is considered. Since humans can be infected by SFV, a seemingly nonpathogenic virus, there is interest in using SFV vectors for human gene therapy. In this regard, detailed understanding of zoonotic SFV infection is highly relevant.
Topics: Animals; Coinfection; Humans; Retroviridae Infections; Spumavirus; Zoonoses
PubMed: 29197389
DOI: 10.1186/s12977-017-0379-9 -
Annual Review of Immunology Apr 2018Retroviruses are genome invaders that have shared a long history of coevolution with vertebrates and their immune system. Found endogenously in genomes as traces of past... (Review)
Review
Retroviruses are genome invaders that have shared a long history of coevolution with vertebrates and their immune system. Found endogenously in genomes as traces of past invasions, retroviruses are also considerable threats to human health when they exist as exogenous viruses such as HIV. The immune response to retroviruses is engaged by germline-encoded sensors of innate immunity that recognize viral components and damage induced by the infection. This response develops with the induction of antiviral effectors and launching of the clonal adaptive immune response, which can contribute to protective immunity. However, retroviruses efficiently evade the immune response, owing to their rapid evolution. The failure of specialized immune cells to respond, a form of neglect, may also contribute to inadequate antiretroviral immune responses. Here, we discuss the mechanisms by which immune responses to retroviruses are mounted at the molecular, cellular, and organismal levels. We also discuss how intrinsic, innate, and adaptive immunity may cooperate or conflict during the generation of immune responses.
Topics: Adaptive Immunity; Animals; Host-Pathogen Interactions; Humans; Immune Evasion; Immune System; Immunity, Innate; Retroviridae; Retroviridae Infections
PubMed: 29328787
DOI: 10.1146/annurev-immunol-051116-052155 -
PLoS Pathogens Feb 2018Tight regulation of immune responses is not only critical for preventing autoimmune diseases but also for preventing immunopathological damage during infections in which... (Review)
Review
Tight regulation of immune responses is not only critical for preventing autoimmune diseases but also for preventing immunopathological damage during infections in which overactive immune responses may be more harmful for the host than the pathogen itself. Regulatory T cells (Tregs) play a critical role in this regulation, which was discovered using the Friend retrovirus (FV) mouse model. Subsequent FV studies revealed basic biological information about Tregs, including their suppressive activity on effector cells as well as the molecular mechanisms of virus-induced Treg expansion. Treg suppression not only limits immunopathology but also prevents complete elimination of pathogens contributing to chronic infections. Therefore, Tregs play a complex role in the pathogenesis of persistent retroviral infections. New therapeutic concepts to reactivate effector T-cell responses in chronic viral infections by manipulating Tregs also came from work with the FV model. This knowledge initiated many studies to characterize the role of Tregs in HIV pathogenesis in humans, where a complex picture is emerging. On one hand, Tregs suppress HIV-specific effector T-cell responses and are themselves targets of infection, but on the other hand, Tregs suppress HIV-induced immune hyperactivation and thus slow the infection of conventional CD4+ T cells and limit immunopathology. In this review, the basic findings from the FV mouse model are put into perspective with clinical and basic research from HIV studies. In addition, the few Treg studies performed in the simian immunodeficiency virus (SIV) monkey model will also be discussed. The review provides a comprehensive picture of the diverse role of Tregs in different retroviral infections and possible therapeutic approaches to treat retroviral chronicity and pathogenesis by manipulating Treg responses.
Topics: Animals; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunosuppression Therapy; Lymphopoiesis; Models, Immunological; Retroviridae; Retroviridae Infections; T-Lymphocytes, Regulatory
PubMed: 29447279
DOI: 10.1371/journal.ppat.1006776 -
Virology Mar 2018Spumaretroviruses, commonly referred to as foamy viruses, are complex retroviruses belonging to the subfamily Spumaretrovirinae, family Retroviridae, which naturally... (Review)
Review
Spumaretroviruses, commonly referred to as foamy viruses, are complex retroviruses belonging to the subfamily Spumaretrovirinae, family Retroviridae, which naturally infect a variety of animals including nonhuman primates (NHPs). Additionally, cross-species transmissions of simian foamy viruses (SFVs) to humans have occurred following exposure to tissues of infected NHPs. Recent research has led to the identification of previously unknown exogenous foamy viruses, and to the discovery of endogenous spumaretrovirus sequences in a variety of host genomes. Here, we describe an updated spumaretrovirus taxonomy that has been recently accepted by the International Committee on Taxonomy of Viruses (ICTV) Executive Committee, and describe a virus nomenclature that is generally consistent with that used for other retroviruses, such as lentiviruses and deltaretroviruses. This taxonomy can be applied to distinguish different, but closely related, primate (e.g., human, ape, simian) foamy viruses as well as those from other hosts. This proposal accounts for host-virus co-speciation and cross-species transmission.
Topics: Animals; Host Specificity; Humans; Phylogeny; Primates; Retroviridae Infections; Spumavirus
PubMed: 29407373
DOI: 10.1016/j.virol.2017.12.035 -
Journal of Clinical Pathology Sep 1987Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us... (Review)
Review
Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Quervain's thyroiditis, multiple sclerosis, acquired hypogammaglobulinaemia, and certain forms of non-A, non-B hepatitis have come under passing suspicion of a retroviral aetiology. With AIDS threatening to become pandemic, and a second AIDS virus appearing in West Africa, human retroviruses are under intensive study for new antiviral drugs targeted to their unique mode of replication, and for the development of vaccines.
Topics: Acquired Immunodeficiency Syndrome; Adult; Cell Transformation, Viral; Deltaretrovirus Infections; Humans; Leukemia, Hairy Cell; Retroviridae Infections; Sarcoma, Kaposi
PubMed: 2889752
DOI: 10.1136/jcp.40.9.1064 -
Viruses Oct 2020Apolipoprotein B mRNA editing enzyme, catalytic peptide 3 (APOBEC3) proteins are critical host proteins that counteract and prevent the replication of retroviruses.... (Review)
Review
Apolipoprotein B mRNA editing enzyme, catalytic peptide 3 (APOBEC3) proteins are critical host proteins that counteract and prevent the replication of retroviruses. Unlike the genome of humans and other species, the mouse genome encodes a single gene, which has undergone positive selection, as reflected by the allelic variants found in different inbred mouse strains. This positive selection was likely due to infection by various mouse retroviruses, which have persisted in their hosts for millions of years. While mouse retroviruses are inhibited by APOBEC3, they nonetheless still remain infectious, likely due to the actions of different viral proteins that counteract this host factor. The study of viruses in their natural hosts provides important insight into their co-evolution.
Topics: Animals; Cytidine Deaminase; Host-Pathogen Interactions; Leukemia Virus, Murine; Mammary Tumor Virus, Mouse; Mice; Retroviridae; Retroviridae Infections; Tumor Virus Infections; Virus Replication
PubMed: 33121095
DOI: 10.3390/v12111217 -
Virology May 2015Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves... (Review)
Review
Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Mice, SCID; Retroviridae; Retroviridae Infections; Virus Latency; Virus Replication
PubMed: 25680625
DOI: 10.1016/j.virol.2015.01.017 -
Retrovirology Oct 2020Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten...
BACKGROUND
Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas with an increased leukemia prevalence at one US zoo, has been associated with other cancers and increased chlamydial disease. To better understand the molecular epidemiology of KoRV variants and the effect of increased viral loads (VLs) on transmissibility and pathogenicity we developed subtype-specific quantitative PCR (qPCR) assays and tested blood and tissue samples from koalas at US zoos (n = 78), two Australian zoos (n = 27) and wild-caught (n = 21) in Australia. We analyzed PCR results with available clinical, demographic, and pedigree data.
RESULTS
All koalas were KoRV-A-infected. A small number of koalas (10.3%) at one US zoo were also infected with non-A subtypes, while a higher non-A subtype prevalence (59.3%) was found in koalas at Australian zoos. Wild koalas from one location were only infected with KoRV-A. We observed a significant association of infection and plasma VLs of non-A subtypes in koalas that died of leukemia/lymphoma and other neoplasias and report cancer diagnoses in KoRV-A-positive animals. Infection and VLs of non-A subtypes was not associated with age or sex. Transmission of non-A subtypes occurred from dam-to-offspring and likely following adult-to-adult contact, but associations with contact type were not evaluated. Brief antiretroviral treatment of one leukemic koala infected with high plasma levels of KoRV-A, -B, and -F did not affect VL or disease progression.
CONCLUSIONS
Our results show a significant association of non-A KoRV infection and plasma VLs with leukemia and other cancers. Although we confirm dam-to-offspring transmission of these variants, we also show other routes are possible. Our validated qPCR assays will be useful to further understand KoRV epidemiology and its zoonotic transmission potential for humans exposed to koalas because KoRV can infect human cells.
Topics: Animals; Animals, Wild; Animals, Zoo; Australia; Female; Gammaretrovirus; Genetic Variation; Male; Molecular Epidemiology; Phascolarctidae; Polymerase Chain Reaction; Prevalence; RNA, Viral; Retroviridae Infections; Tumor Virus Infections; United States; Viral Load
PubMed: 33008414
DOI: 10.1186/s12977-020-00541-1