anti-retrovirus

UNLABELLED: Previously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactions in vitro. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particles in vitro, we infer that RSV Gag is biologically active...

The primary function of white adipose tissues is to store excess energy. The current study aimed to investigate the roles of Gremlin 2 (Grem2), a glycoprotein in adipogenesis. Using polymerase chain reaction‑based microarrays, it was determined that Grem2 was markedly downregulated in adipose tissues from obese animals and humans. In addition, 3T3‑L1 cells were used to investigate the details of the mechanisms underlying the anti‑adipogenic effects of Grem2. Grem2 expression was markedly decreased upon the induction of adipocyte differentiation, as demonstrated by reverse transcription‑quantitative polymerase chain reaction and western blot analysis...

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial...

Apoptotic cells generated during development and immune responses in animals are rapidly engulfed by phagocytes, such as macrophages and dendritic cells. When the engulfment process malfunctions, the apoptotic cells undergo secondary necrosis, which results in the release of noxious cellular components into the extracellular space. Thus, the efficient clearance of apoptotic cells is indispensable for the maintenance of tissue homeostasis; however, the molecular mechanisms underlying the engulfment of apoptotic cells remain largely unknown...

Extensive work on experimental animal models clearly demonstrates that infectious agents can break immunological tolerance to self-antigens and induce autoimmune disorders, mainly systemic lupus erythematosus (SLE). The establishment of a causative link between infections and autoimmunity has been largely studied in a host of clinical studies, proving the role of infectious agents in the induction, as well as in the progression or exacerbation of SLE. However, we are far from a plain understanding of microbial-host interactions in the pathogenesis of SLE...

BACKGROUND: It is well established that effector T cell responses are crucial for the control of most virus infections, but they are often tightly controlled by regulatory T cells (Treg) to minimize immunopathology. NK cells also contribute to virus control but it is not known if their antiviral effect is influenced by virus-induced Tregs as well. We therefore analyzed whether antiretroviral NK cell functions are inhibited by Tregs during an acute Friend retrovirus infection of mice. RESULTS: Selective depletion of Tregs by using the transgenic DEREG mouse model resulted in improved NK cell proliferation, maturation and effector cell differentiation...

GNbAC1 is a humanized monoclonal antibody targeting MSRV-Env, an endogenous retroviral protein, which is expressed in multiple sclerosis (MS) lesions, is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. This paper describes the open-label extension up to 12months of a trial testing GNbAC1 in 10 MS patients at 2 and 6mg/kg. The primary objective was to assess GNbAC1 safety, and other objectives were pharmacokinetic and pharmacodynamic assessments. During the extended study, no safety issues occurred in the 8 remaining patients...

Myogenesis is defined as growth, differentiation and repair of muscles where cell fusion of myoblasts to multinucleated myofibers is one major characteristic. Other cell fusion events in humans are found with bone resorbing osteoclasts and placental syncytiotrophoblasts. No unifying gene regulation for natural cell fusions has been found. We analyzed skeletal muscle biopsies of competitive cyclists for muscle-specific attributes and expression of human endogenous retrovirus (ERV) envelope genes due to their involvement in cell fusion of osteoclasts and syncytiotrophoblasts...

The enzyme reverse transcriptase (RT) was discovered in retroviruses almost 50 years ago. The demonstration that other types of viruses, and what are now called retrotransposons, also replicated using an enzyme that could copy RNA into DNA came a few years later. The intensity of the research in both the process of reverse transcription and the enzyme RT was greatly stimulated by the recognition, in the mid-1980s, that human immunodeficiency virus (HIV) was a retrovirus and by the fact that the first successful anti-HIV drug, azidothymidine (AZT), is a substrate for RT...

Current HIV-1 gene therapy approaches aim at stopping the viral life cycle at its earliest steps, such as entry or immediate postentry events. Among the most widely adopted strategies are CCR5 downregulation/knockout and the use of broadly neutralizing antibodies. However, the long-term efficacy and side effects are still unclear. TRIM5α is an interferon-stimulated restriction factor that can intercept incoming retroviruses within one hour of cytosolic entry and potently inhibit the infectivity of restriction-sensitive viruses...

Intrinsic immunity describes the set of recently discovered but poorly understood cellular mechanisms that specifically target viral pathogens. Their discovery derives in large part from intensive studies of HIV and SIV that revealed restriction factors acting at various stages of the retroviral life cycle. Recent studies indicate that some factors restrict both retroviruses and retrotransposons but surprisingly in ways that may differ. We screened known interferon-stimulated antiviral proteins previously untested for their effects on cell culture retrotransposition...

We have previously shown that Toll-like receptor (TLR) agonists contribute to the control of viral infection by augmenting virus-specific CD8(+) T-cell responses. It is also well established that signaling by TLRs results in the production of pro-inflammatory cytokines such as interleukin 6 (IL-6). However, how these pro-inflammatory cytokines influence the virus-specific CD8(+) T-cell response during the TLR agonist stimulation remained largely unknown. Here, we investigated the role of TLR-induced IL-6 in shaping virus-specific CD8(+) T-cell responses in the Friend retrovirus (FV) mouse model...

Acyclic nucleoside phosphonates (ANPs) are potent antiviral agents effective against replication of DNA viruses and retroviruses including human immunodeficiency virus (HIV). Prototype compound 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir) is a principal component of drugs widely used in the treatment of HIV infection (Viread, Truvada). Besides their antimetabolic mode of action, ANPs possess immunomodulatory properties. A number of them have been previously found to stimulate secretion of cytokines and anti-HIV effective chemokines...

INTRODUCTION: The invariant natural killer T (iNKT) cell has been shown to play a central role in early stages immune responses against Mycobacterium tuberculosis (Mtb) infection, which become nonresponsive (anergic) and fails to control the growth of Mtb in patients with active tuberculosis. Enhancement of iNKT cell responses to Mtb antigens can help to resist infection. STUDY DESIGN AND METHODS: In the present study, an Mtb 38-kDa antigen-specific T cell receptor (TCR) was isolated from human CD8(+) T cells stimulated by 38-kDa antigen in vitro, and then transduced into primary iNKT cells by retrovirus vector...

The article presents analysis of activities concerning organization of pre-analytic stage of monitoring of HIV resistance to anti- retrovirus preparations on territories of the Privolzhskiy Federal Okrug. The medical records of patients receiving anti-retrovirus therapy and appointment cards to detect drug resistance of HIV from territorial centers of prevention and control of AIDS and infectious diseases are analyzed. The results of testing of specialists of service of prevention of AIDS/HIV with questionnaire "Characteristics of pre-analytical stage under implementation of molecular genetic and immunologic analyses" developed in the Privolzhskiy okrug center of prevention and control ofAIDS and samples of bio-tests obtained during coming-outs in regions of okrug were included into analysis too...

Intrinsic restriction factors and viral nucleic acid sensors are important for the anti-viral response. Here, we show how upstream sensing of retroviral reverse transcripts integrates with the downstream effector APOBEC3, an IFN-induced cytidine deaminase that introduces lethal mutations during retroviral reverse transcription. Using a murine leukemia virus (MLV) variant with an unstable capsid that induces a strong IFNβ antiviral response, we identify three sensors, IFI203, DDX41, and cGAS, required for MLV nucleic acid recognition...

A human betaretrovirus resembling mouse mammary tumor virus has been characterized in patients with primary biliary cirrhosis. The agent triggers a disease-specific phenotype in vitro with aberrant cell-surface expression of mitochondrial antigens. The presentation of a usually sequestered self-protein is thought to lead to the loss of tolerance and the production of anti-mitochondrial antibodies associated with the disease. Similar observations have been made in mouse models, where mouse mammary tumor virus infection has been linked with the development of cholangitis and production of anti-mitochondrial antibodies...

AIMS: The present study addresses the issue of enhanced apoptotic response to AZT following co-treatment with an NF-kB inhibitor. MAIN METHODS: To investigate this issue, different cell lines were assayed for susceptibility to AZT-mediated apoptosis without or with the addition of the NF-kB inhibitor Bay-11-7085. For further investigation, U937 cells were selected as good-responder cells to the combination treatment with 32 or 128 μM AZT, and 1 μM Bay-11-7085...

Therapeutic vaccinations have a potential application in infections where no curative treatment is available. In contrast to HIV, efficacious vaccines for a cat retrovirus, feline leukemia virus (FeLV), are commercially available. However, the infection is still prevalent, and no effective treatment of the infection is known. By vaccinating persistently FeLV-infected cats and presenting FeLV antigens to the immune system of the host, e.g., in the form of recombinant and/or adjuvanted antigens, we intended to shift the balance toward an advantage of the host so that persistent infection could be overcome by the infected cat...

BACKGROUND AND OBJECTIVE: The liver-specific functions of hepatocytes are improved by co-culturing hepatocytes with primary hepatic stellate cells (HSC). However, primary HSC have a short lifespan in vitro, which is considered a major limitation for their use in various applications. This study aimed to establish immortalized human HSC using the simian virus 40 large T antigen (SV40LT) for applications in co-culturing with hepatocytes and HSC in vitro. METHODS: Primary human HSC were transfected with a recombinant retrovirus containing SV40LT...