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Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV mac251 challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV mac251 . Strong protection...
To establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic...
Vaccinia virus (VV) K1L is a host-range gene and encodes a protein comprised of six ankyrin repeats (ANKs). We showed here that a large portion of the K1L protein, except ankyrin repeat 1 (ANK1) and C-terminal halves of ANK2 and ANK3, can be deleted or substituted with an unrelated ANK with no adverse effect on VV replication in human HeLa cells. In contrast, only ANK4 and ANK6 can be mutated without...
The nucleocapsid (NC) protein from HIV-1 contains two zinc-fingers, both of which are necessary for virus replication. This is the first in-depth study that presents the effects of nucleocapsid zinc-finger substitutions on the kinetics of reverse transcription and integration. Over a 72-h time-course of infection, the quantities of viral DNA (vDNA) observed with viruses containing either the nucleocapsid...
The human glucose transporter protein 1 (GLUT-1) functions as a receptor for human T cell leukemia virus (HTLV). GLUT-1 is a twelve-transmembrane cell surface receptor with six extracellular (ECL) and seven intracellular domains. To analyze HTLV-1 cytotropism, we utilized polyclonal antibodies to a synthetic peptide corresponding to the large extracellular domain of GLUT-1. The antibodies caused significant...
DNA shuffling and screening technologies were used to produce chimeric DNA constructs expressing antigens that shared epitopes from all four dengue serotypes. Three shuffled constructs (sA, sB and sC) were evaluated in the rhesus macaque model. Constructs sA and sC expressed pre-membrane and envelope genes, whereas construct sB expressed only the ectodomain of envelope protein. Five of six, and four...
In a small sample of 57 retrovirus integration sites (RISs) isolated from 23 end-stage lymphomas induced in NMRI mice by the B-lymphotropic Akv wt or an enhancer mutant hereof, Akv1–99, we identified 14 novel RISs and defined 9 novel CISs (common insertion sites). Moreover, when comparing with RISs from tumors induced by the T-lymphomagenic SL3-3, we observed that SL3-3 targets RefSeq promoter regions...
Chronic γ-herpesvirus infection is a dynamic process involving latent infection, reactivation from latency, and low level persistent replication. The γ-herpesviruses maintain latent infection in restricted subsets of hematopoietic cells as a result of an intricate balance between host factors that suppress infection and viral factors that facilitate evasion of the immune response. Immune effectors...
The arenavirus family contains several important human pathogens including Lassa fever virus (LASV), lymphocytic choriomeningitis virus (LCMV) and the New World clade B viruses Junin (JUNV) and Machupo (MACV). Previously, α-dystroglycan (α-DG) was identified as a receptor recognized by LASV and certain strains of LCMV. However, other studies have suggested that α-DG is probably not used by the clade...
The coiled-coil domain of the tripartite motif (TRIM) family protein TRIM5α is required for trimerization and function as an antiretroviral restriction factor. Unlike the coiled-coil regions of other related TRIM proteins, the coiled coil of TRIM5α is not sufficient for multimerization. The linker region between the coiled-coil and B30.2 domains is necessary for efficient TRIM5α trimerization. Most...
Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs through the activation of a subset of transcription factors, including Interferon Regulatory Factor (IRF)-3. In this study, we have investigated the signaling pathway leading to RSV-induced IRF-3 activation and whether it is mediated by intracellular reactive oxygen species (ROS) generation. Our results show that RSV infection...
We investigated possible interactions between HIV-1 receptor (CD4) and the main coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells form a complex that can be immunoprecipitated with antibodies directed against the extracellular domain of either protein. Mutagenesis revealed that the CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the cytoplasmic...
Persistent infections with human papillomaviruses type 18 can result in the development of cervical cancer. HPV18 genomes persist extrachromosomally in low-grade and precancerous lesions but are always integrated in cervical cancers, and this might contribute to the progression of HPV18-induced lesions. To address whether integration induces additional changes in host cells, several keratinocyte lines...
Mimivirus, a parasite of Acanthamoeba polyphaga, is the largest DNA virus known; it encodes a cornucopia of proteins with imputed functions in DNA replication, modification, and repair. Here we produced, purified, and characterized mimivirus DNA ligase (MimiLIG), an NAD + -dependent nick joining enzyme homologous to bacterial LigA and entomopoxvirus DNA ligase. MimiLIG is a 636-aa polypeptide...
The Reoviridae have double-stranded RNA genomes of 10–12 segments, each in a single copy in the mature virion. The basis of genome segment sorting during virus assembly that ensures each virus particle contains the complete viral genome is unresolved. Bluetongue virus (BTV) NS2 is a single-stranded RNA-binding protein that forms inclusion bodies in infected cells. Here, we demonstrate that the specific...
Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness...
In this report, we have studied gene expression profiles in human primary lung fibroblasts (IMR-90) during the very early phase of an adenovirus infection. Eight out of twelve genes with known functions encoded transcription factors linked to two major cellular processes; inhibition of cell growth (ATF3, ATF4, KLF4, KLF6 and ELK3) and immune response (NR4A1 and CEBPB), indicating that the earliest...
The major histocompatibility complex (MHC) class I region in mammals contains both classical and non-classical MHC class I genes. Classical MHC class I molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non-classical MHC class I molecules have a variety of functions. Both classical and non-classical MHC molecules interact with natural killer cell receptors and may under some...
Development of an effective vaccine for severe acute respiratory syndrome (SARS) remains to be a priority to prevent possible re-emergence of SARS coronavirus (SARS-CoV). We previously demonstrated that the receptor-binding domain (RBD) of SARS-CoV S protein is a major target of neutralizing antibodies. This suggests that the RBD may serve as an ideal vaccine candidate. Recombinant adeno-associated...
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