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Viruses Apr 2022Immunocompromise is a common condition in cats, especially due to widespread infections with immunosuppressive viruses, such as feline immunodeficiency virus (FIV) and... (Review)
Review
Immunocompromise is a common condition in cats, especially due to widespread infections with immunosuppressive viruses, such as feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), but also due to chronic non-infectious diseases, such as tumours, diabetes mellitus, and chronic kidney disease, as well as treatment with immunosuppressive drugs, such as glucocorticoids, cyclosporins, or tumour chemotherapy. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from eleven European countries, discusses the current knowledge and rationale for vaccination of immunocompromised cats. So far, there are few data available on vaccination of immunocompromised cats, and sometimes studies produce controversial results. Thus, this guideline summarizes the available scientific studies and fills in the gaps with expert opinion, where scientific studies are missing. Ultimately, this review aims to help veterinarians with their decision-making in how best to vaccinate immunocompromised cats.
Topics: Animals; Cats; Europe; Immunodeficiency Virus, Feline; Leukemia Virus, Feline; Vaccination
PubMed: 35632665
DOI: 10.3390/v14050923 -
Biotechnology Journal Jan 2021Lentiviral vectors (LVs) have been increasingly used as a tool for gene and cell therapies since they can stably integrate the genome in dividing and nondividing cells.... (Review)
Review
Lentiviral vectors (LVs) have been increasingly used as a tool for gene and cell therapies since they can stably integrate the genome in dividing and nondividing cells. LV production and purification processes have evolved substantially over the last decades. However, the increasing demands for higher quantities with more restrictive purity requirements are stimulating the development of novel materials and strategies to supply the market with LV in a cost-effective manner. A detailed review of each downstream process unit operation is performed, limitations, strengths, and potential outcomes being covered. Currently, the majority of large-scale LV manufacturing processes are still based on adherent cell culture, although it is known that the industry is migrating fast to suspension cultures. Regarding the purification strategy, it consists of batch chromatography and membrane technology. Nevertheless, new solutions are being created to improve the current production schemes and expand its clinical use.
Topics: Cell Culture Techniques; Chromatography, Ion Exchange; Genetic Vectors; HEK293 Cells; Humans; Lentivirus
PubMed: 33089626
DOI: 10.1002/biot.202000019 -
Nature Reviews. Microbiology Jan 2022A hallmark of retroviral replication is establishment of the proviral state, wherein a DNA copy of the viral RNA genome is stably incorporated into a host cell... (Review)
Review
A hallmark of retroviral replication is establishment of the proviral state, wherein a DNA copy of the viral RNA genome is stably incorporated into a host cell chromosome. Integrase is the viral enzyme responsible for the catalytic steps involved in this process, and integrase strand transfer inhibitors are widely used to treat people living with HIV. Over the past decade, a series of X-ray crystallography and cryogenic electron microscopy studies have revealed the structural basis of retroviral DNA integration. A variable number of integrase molecules congregate on viral DNA ends to assemble a conserved intasome core machine that facilitates integration. The structures additionally informed on the modes of integrase inhibitor action and the means by which HIV acquires drug resistance. Recent years have witnessed the development of allosteric integrase inhibitors, a highly promising class of small molecules that antagonize viral morphogenesis. In this Review, we explore recent insights into the organization and mechanism of the retroviral integration machinery and highlight open questions as well as new directions in the field.
Topics: Crystallography, X-Ray; DNA, Viral; HIV Integrase; HIV-1; Humans; Integrases; Models, Molecular; Protein Conformation; Retroviridae; Virus Integration
PubMed: 34244677
DOI: 10.1038/s41579-021-00586-9 -
Journal of Feline Medicine and Surgery Sep 2020Feline leukaemia virus (FeLV) is a retrovirus of domestic cats worldwide. Cats lacking strong FeLV-specific immunity and undergoing progressive infection commonly... (Review)
Review
PRACTICAL RELEVANCE
Feline leukaemia virus (FeLV) is a retrovirus of domestic cats worldwide. Cats lacking strong FeLV-specific immunity and undergoing progressive infection commonly develop fatal FeLV-associated disease. Many aspects of FeLV infection pathogenesis have been elucidated, some during more recent years using molecular techniques. It is recommended that the FeLV status of every cat is known, since FeLV infection can influence the prognosis and clinical management of every sick cat. Moreover, knowledge of a cat's FeLV status is of epidemiological importance to prevent further spread of the infection.
CLINICAL CHALLENGES
Diagnosing FeLV infection remains challenging due to different outcomes of infection, which can vary over time depending on the balance between the virus and the host's immune system. Furthermore, testing for FeLV infection has become more refined over the years and now includes diagnostic assays for different viral and immunological parameters. Knowledge of FeLV infection pathogenesis, as well as the particulars of FeLV detection methods, is an important prerequisite for correct interpretation of any test results and accurate determination of a cat's FeLV status.
AIMS
The current review presents recent knowledge on FeLV pathogenesis, key features to be determined in FeLV infection, and frequently used FeLV detection methods, and their characteristics and interpretation. An algorithm for the diagnosis of FeLV infection in a single cat, developed by the European Advisory Board on Cat Diseases, is included, and FeLV testing in specific situations is addressed. As well as increasing awareness of this deadly infection in domestic cats, the aim is to contribute diagnostic expertise to allow veterinarians in practice to improve their recognition, and further reduce the prevalence, of FeLV infection.
Topics: Animals; Cat Diseases; Cats; Leukemia Virus, Feline; Retroviridae Infections; Tumor Virus Infections
PubMed: 32845225
DOI: 10.1177/1098612X20941785 -
Annual Review of Immunology Apr 2023Our defenses against infection rely on the ability of the immune system to distinguish invading pathogens from self. This task is exceptionally challenging, if not... (Review)
Review
Our defenses against infection rely on the ability of the immune system to distinguish invading pathogens from self. This task is exceptionally challenging, if not seemingly impossible, in the case of retroviruses that have integrated almost seamlessly into the host. This review examines the limits of innate and adaptive immune responses elicited by endogenous retroviruses and other retroelements, the targets of immune recognition, and the consequences for host health and disease. Contrary to theoretical expectation, endogenous retroelements retain substantial immunogenicity, which manifests most profoundly when their epigenetic repression is compromised, contributing to autoinflammatory and autoimmune disease and age-related inflammation. Nevertheless, recent evidence suggests that regulated immune reactivity to endogenous retroelements is integral to immune system development and function, underpinning cancer immunosurveillance, resistance to infection, and responses to the microbiota. Elucidation of the interaction points with endogenous retroelements will therefore deepen our understanding of immune system function and contribution to disease.
Topics: Humans; Animals; Retroelements; Immunity, Innate; Autoimmune Diseases; Retroviridae
PubMed: 36630597
DOI: 10.1146/annurev-immunol-101721-033341 -
Viruses May 2022This review is an accompaniment to a Special Issue on "Retroviral RNA Processing". It discusses post-transcriptional regulation of retroviruses, ranging from the ancient... (Review)
Review
This review is an accompaniment to a Special Issue on "Retroviral RNA Processing". It discusses post-transcriptional regulation of retroviruses, ranging from the ancient foamy viruses to more modern viruses, such as HIV-1, HTLV-1, Rous sarcoma virus, murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus. This review is not comprehensive. However, it tries to address some of the major questions in the field with examples of how different retroviruses express their genes. It is amazing that a single primary RNA transcript can have so many possible fates: genomic RNA, unspliced mRNA, and up to 50 different alternatively spliced mRNAs. This review will discuss the sorting of RNAs for packaging or translation, RNA nuclear export mechanisms, splicing, translation, RNA modifications, and avoidance of nonsense-mediated RNA decay.
Topics: Active Transport, Cell Nucleus; Animals; Leukemia Virus, Murine; Mice; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Viral; Retroviridae
PubMed: 35632854
DOI: 10.3390/v14051113 -
The Lancet. Infectious Diseases May 2021
Topics: Congresses as Topic; Female; HIV Infections; Ill-Housed Persons; Humans; Male; Opportunistic Infections; Pre-Exposure Prophylaxis; Retroviridae; Retroviridae Infections; Sex Workers; Sexually Transmitted Diseases; Transgender Persons
PubMed: 33894841
DOI: 10.1016/S1473-3099(21)00214-0 -
Annual Review of Virology Sep 2019I always loved biology and to do experiments. This passion and a great deal of good fortune and serendipity landed me in the field of retrovirology at the time when it... (Review)
Review
I always loved biology and to do experiments. This passion and a great deal of good fortune and serendipity landed me in the field of retrovirology at the time when it opened to experimental analysis. I became involved in viral replication, genetics, and viral oncogenes. In more recent years, I have applied what I learned in tumor virology to human cancer. The early years of my personal life were marked by displacements and migration: deportation into East Germany, escape to the West, and emigration to the United States. As a young man I faced heartbreaking personal tragedies but attained a peaceful and steady course in the second half of my life. I am fortunate to have found my home in Southern California and to continue in cancer research.
Topics: Germany; History, 20th Century; History, 21st Century; Humans; Oncogenes; Oncogenic Viruses; Retroviridae; United States; Viruses
PubMed: 31567064
DOI: 10.1146/annurev-virology-092818-015828 -
Viruses Jan 2022Stephen Oroszlan received his early education in Hungary, graduating in 1950 from the Technical University in Budapest with a degree in chemical engineering [...].
Stephen Oroszlan received his early education in Hungary, graduating in 1950 from the Technical University in Budapest with a degree in chemical engineering [...].
Topics: History, 20th Century; History, 21st Century; Humans; Male; Retroviridae; Retroviridae Proteins; Viral Protease Inhibitors; Viral Proteases
PubMed: 35215882
DOI: 10.3390/v14020290 -
Frontiers in Immunology 2022HTLV-1 is an oncovirus causing ATL and other inflammatory diseases such as HAM/TSP and HU in about 5% of infected individuals. It is also known that HTLV-1-infected... (Review)
Review
HTLV-1 is an oncovirus causing ATL and other inflammatory diseases such as HAM/TSP and HU in about 5% of infected individuals. It is also known that HTLV-1-infected cells maintain a disease-free, immortalized, latent state throughout the lifetimes of about 95% of infected individuals. We believe that the stable maintenance of disease-free infected cells in the carrier is an intrinsic characteristic of HTLV-1 that has been acquired during its evolution in the human life cycle. We speculate that the pathogenesis of the virus is ruled by the orchestrated functions of viral proteins. In particular, the regulation of Rex, the conductor of viral replication rate, is expected to be closely related to the viral program in the early active viral replication followed by the stable latency in HTLV-1 infected T cells. HTLV-1 and HIV-1 belong to the family and share the same tropism, e.g., human CD4 T cells. These viruses show significant similarities in the viral genomic structure and the molecular mechanism of the replication cycle. However, HTLV-1 and HIV-1 infected T cells show different phenotypes, especially in the level of virion production. We speculate that how the activity of HTLV-1 Rex and its counterpart HIV-1 Rev are regulated may be closely related to the properties of respective infected T cells. In this review, we compare various pathological aspects of HTLV-1 and HIV-1. In particular, we investigated the presence or absence of a virally encoded "regulatory valve" for HTLV-1 Rex or HIV-1 Rev to explore its importance in the regulation of viral particle production in infected T cells. Finally, wereaffirm Rex as the key conductor for viral replication and viral pathogenesis based on our recent study on the novel functional aspects of Rex. Since the activity of Rex is closely related to the viral replication rate, we hypothesize that the "regulatory valve" on the Rex activity may have been selectively evolved to achieve the "scenario" with early viral particle production and the subsequent long, stable deep latency in HTLV-1 infected cells.
Topics: Gene Products, rex; Gene Products, tax; HIV-1; Human T-lymphotropic virus 1; Humans; Viral Proteins; Virus Replication
PubMed: 36189216
DOI: 10.3389/fimmu.2022.959962