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The endocytic pathway for human immunodeficiency virus infection.

We have presented data supporting the view that HIV infection of T cells and monocytes proceeds via receptor-mediated endocytosis. Biochemic … enriched in cholesterol, a property not associated with the plasma membrane but clearly involved in Semliki Forest virus fusion within the endosome.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of a culturable fungal species and endosymbiotic bacteria in saliva of Aedes aegypti and Culex pipiens and their impact on arbovirus infection in vitro.

BACKGROUND: Mosquito saliva plays a key role in arbovirus transmission and pathogenesis. It was shown that saliva contains several molecules … n of bacteria or fungi present in the mosquito saliva. Notably, co-incubation of the mosquito-borne Semliki Forest virus with saliva from antibiotic- or antifungal-treated mosquitoes triggered a decrease in viral infection in human skin fibroblasts compared with nontreated saliva. CONCLUSIONS: These findings indicate that bacteria and fungi can be present in mosquito …

Targeting conserved interaction surfaces of alphavirus nsP4 supports the rational design of live-attenuated vaccine candidates.

UNLABELLED: Alphaviruses are emerging arboviruses that pose a growing threat to global public health; however, effective interventions remai … system. Sixteen selected mutations were further analyzed in a CHIKV-o'nyong-nyong virus chimera and Semliki Forest virus (SFV). Most mutants were viable but showed varying degrees of attenuation in mammalian and mosquito cells. Viruses carrying mutations in predicted RNA-interaction sites frequently acquired pseudoreversions and/or second-site compensatory changes, wh …

Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assays based on recombinant TBEV subviral particles.

Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with … MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions o …

A Simplified SARS-CoV-2 Mouse Model Demonstrates Protection by an Oral Replicon-Based mRNA Vaccine.

A mouse model of SARS-CoV-2 that can be developed in any molecular biology lab with standard facilities will be valuable in evaluating drugs … R), membrane glycoprotein (M) and epitopes of nsp13 of parental SARS-CoV-2. Further, Salmonella and Semliki Forest virus replicon were exploited, respectively, for gene delivery and mRNA expression. We recorded potent cross-protective neutralizing antibodies in immunized mice against the SARS-CoV-2 delta variant. The vaccine protected the mice against viral replicatio …

Recombinant human prion protein mutants huPrP D178N/M129 (FFI) and huPrP+9OR (fCJD) reveal proteinase K resistance.

The Semliki-Forest virus (SFV) system was used to overexpress human wild-type and mutant prion proteins as well as FLAG-tagged human and bovine PrP in mammalian cells. The application of recombinant SFV vectors allowed a high-level production of highly glycosylated prion proteins with a molecular weight ranging from 25 to 30 kDa for recombinant wild-type human PrP and from 26 to 32 kDa for wild-type bovine PrP. Further, we report here the generation of recombinant mutant prion proteins that are associated with inherited human prion diseases such as fatal familial insomnia (FFI) and Creutzfeldt

Functional role of type I and type II interferons in antiviral defense.

Mice lacking the known subunit of the type I interferon (IFN) receptor were completely unresponsive to type I IFNs, suggesting that this receptor chain is essential for type I IFN-mediated signal transduction. These mice showed no overt anomalies but were unable to cope with viral infections, despite otherwise normal immune responses. Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant.

Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40). Relevance to Alzheimer's disease.

Population studies have established that one of the common isoforms of apolipoprotein E, the apoE4, is associated with higher incidence and … nascent apoE isoforms we have expressed their cDNAs in baby hamster kidney (BHK-21) cells using the Semliki Forest Virus expression system. Analysis of the secreted apoE by one- and two-dimensional gel electrophoresis and immunoblotting showed that the nascent apoE is heavily modified with carbohydrate chains containing sialic acid. A dimeric form of apoE is formed wi …

A novel self-amplified RNA vaccine co-expressing NA and HA1 delivered by Salmonella confers potent protection against H9N2 influenza in chickens.

The ongoing evolution of the H9N2 avian influenza virus presents a growing threat to both the poultry industry and public health. In this context, vaccination is not only a vital preventive measure but also the primary strategy for controlling viral transmission and preventing outbreaks. To enhance vaccine efficacy, this study successfully established a novel self-amplified RNA vaccine platform utilizing the Semliki Forest virus (SFV) replicon. The core mechanism involves utilizing the CAG promoter to drive the expression of SFV RNA-dependent RNA polymerase (RdRp), which initiates the autonomo…

A novel oral vaccine strategy utilizing a plasmid with CAG promoter-driven alphavirus RdRp for Co-expression of NA epitope and adjuvant in attenuated Salmonella boosts immune responses against H9N2 in mice.

The ongoing evolution of H9N2 avian influenza virus continues to pose a significant threat to the poultry industry and overall biosecurity. Vaccination remains the primary strategy for controlling this pathogen. To develop more effective vaccines, this study employed a novel self-amplified RNA-encoding plasmid system previously constructed based on the Semliki Forest virus (SFV) replicon. This system utilizes the CAG promoter to drive the expression of SFV RNA-dependent RNA polymerase, which initiates the autonomous replication of mRNA that encodes the target gene. This process enables efficie…

Endemic and Epidemic Human Alphavirus Infections in Eastern Panama: An Analysis of Population-Based Cross-Sectional Surveys.

Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic

Viral Vector-Based Melanoma Gene Therapy.

Gene therapy applications of oncolytic viruses represent an attractive alternative for cancer treatment. A broad range of oncolytic viruses, including adenoviruses, adeno-associated viruses, alphaviruses, herpes simplex viruses, retroviruses, lentiviruses, rhabdoviruses, reoviruses, measles virus, Newcastle disease virus, picornaviruses and poxviruses, have been used in diverse preclinical and clinical studies for the treatment of various diseases, including colon, head-and-neck, prostate and breast cancer as well as squamous cell carcinoma and glioma. The majority of studies have focused on i

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… Oncolytic capacity of attenuated replicative semliki forest virus in human melanoma xenografts in severe combined immunodeficient mice. Cancer Res. 2006;66:7185–7194. doi: 10.1158/0008-5472.CAN-05-2214. 61. … Oncolytic Semliki forest virus vector as a novel candidate against unresectable osteosarcoma. Cancer Res. 2008;68:8342–8350. doi: 10.1158/0008-5472.CAN-08-0251. 63. Venticinque L., Meruelo D. …

Bortezomib inhibits chikungunya virus replication by interfering with viral protein synthesis.

Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness accompanied by myalgia and arthralgia. Despite having re-emerged as a significant public health threat, there are no approved therapeutics or prophylactics for CHIKV infection. In this study, we explored the anti-CHIKV effects of proteasome inhibitors and their potential mechanism of antiviral action. A panel of proteasome inhibitors with different functional groups reduced CHIKV infectious titers in a dose-dependent manner. Bortezomib, which has been FDA-approved for multiple myeloma and mantle cell lymphoma, was further

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… CHIKV is part of the Old World alphaviruses, which also include the well-studied model viruses, Semliki Forest virus (SFV) and Sindbis virus (SINV) [ 13 ]. Chikungunya virions are enveloped, with a positive-sense RNA genome enclosed within a nucleocapsid core [ 12 ]. … Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease. J Gen Virol. 2001;82(Pt 4):765–73. 10.1099/0022-1317-82-4-765 43. Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, et al. …

Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis.

The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current un

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… Virus titres and persistently raised white cell counts in cerebrospinal fluid in mice after peripheral infection with demyelinating Semliki Forest virus. Neuropathol. Appl. Neurobiol. 8 395 – 401 10.1111/j.1365-2990.1982.tb00307.x 6294545 Polianova M. T. Ruscetti F. W. Pert C. B. Ruff M. … Forest virus Sindbis virus tick borne encephalitis virus toll-like receptor tumor necrosis factor alpha Venezuelan equine encephalitis virus Western equine encephalitis virus West Nile virus …

Trial watch: Oncolytic viruses for cancer therapy.

Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several diffe

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… KW Oshiro EM Viola JJ DeVroom HL Otto E Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells Nat Med 1997 3 1354 61 10.1038/nm1297-1354 9396605 66 Smyth JW Fleeton MN Sheahan BJ Atkins GJ Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki … Forest virus and its derived vector Gene Ther 2005 12 147 59 10.1038/sj.gt.3302390 15372069 67 Vähä-Koskela MJ Kallio JP Jansson LC Heikkilä JE Zakhartchenko VA Kallajoki MA Oncolytic capacity of attenuated replicative semliki forest virus in human melanoma xenografts in severe combined immunodeficient …

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of infected-coronavirus cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to establ