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Virus

About: Virus is a research topic. Over the lifetime, 136914 publications have been published within this topic receiving 5209107 citations. The topic is also known as: infectious agent & viruses.


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Journal ArticleDOI
TL;DR: AAV vectors do efficiently promote in vivo gene transfer to the airway epithelium which is stable over several months and indicates that AAV-CFTR vectors could potentially be very useful for gene therapy.
Abstract: Adeno-associated virus (AAV) vectors expressing the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA complement the cystic fibrosis (CF) defect in vitro. Unlike other DNA virus vectors, AAV is a stably integrating virus, which could make possible long-term in vivo complementation of the CF defect in the airway epithelium. We report AAV-CFTR gene transfer and expression after infection of primary CF nasal polyp cells and after in vivo delivery of AAV-CFTR vector to one lobe of the rabbit lung through a fiberoptic bronchoscope. In the rabbit, vector DNA could be detected in the infected lobe up to 6 months after administration. A 26-amino acid polypeptide sequence unique to the recombinant AAV-CFTR protein was used to generate both oligonucleotide probes and a polyclonal antibody which allowed the unambiguous identification of vector RNA and CFTR protein expression. With these reagents, CFTR RNA and protein were detected in the airway epithelium of the infected lobe for up to 6 months after vector administration. AAV vectors do, therefore, efficiently promote in vivo gene transfer to the airway epithelium which is stable over several months. These findings indicate that AAV-CFTR vectors could potentially be very useful for gene therapy.

563 citations

Journal ArticleDOI
TL;DR: A critical function for Ncr1 is demonstrated in the in vivo eradication of influenza virus, and accumulation of natural killer cells at the site of influenza infection is noted by tracking the green fluorescent protein.
Abstract: The elimination of viruses and tumors by natural killer cells is mediated by specific natural killer cell receptors. To study the in vivo function of a principal activating natural killer cell receptor, NCR1 (NKp46 in humans), we replaced the gene encoding this receptor (Ncr1) with a green fluorescent protein reporter cassette. There was enhanced spread of certain tumors in 129/Sv but not C57BL/6 Ncr1(gfp/gfp) mice, and influenza virus infection was lethal in both 129/Sv and C57BL/6 Ncr1(gfp/gfp) mice. We noted accumulation of natural killer cells at the site of influenza infection by tracking the green fluorescent protein. Our results demonstrate a critical function for Ncr1 in the in vivo eradication of influenza virus.

563 citations

Journal ArticleDOI
16 Aug 1990-Nature
TL;DR: It is now shown that viruses can in principle escape the immunosurveillance of virus-specific cytotoxic T cells by mutations that alter the relevant T-cell epitope.
Abstract: Viruses persist in an immune population, as in the case of influenza, or in an individual, as postulated for human immunodeficiency virus, when they are able to escape existent neutralizing antibody responses by changing their antigens. It is now shown that viruses can in principle escape the immunosurveillance of virus-specific cytotoxic T cells by mutations that alter the relevant T-cell epitope.

562 citations

Journal ArticleDOI
07 Jan 1988-Nature
TL;DR: An efficient expression system is described in which a recombinant, soluble form of CD4 (sCD4) is secreted into tissue culture supernatants and binds to the envelope glycoprotein (gpllO) of HIV and inhibits the binding of virus to CD4+ lymphocytes, resulting in a striking inhibition of virus infectivity.
Abstract: CD4 (T4) is a glycoprotein of relative molecular mass 55,000 (Mr 55K) on the surface of T lymphocytes which is thought to interact with class II MHC (major histocompatibility complex) molecules, mediating efficient association of helper T cells with antigen-bearing targets. The CD4 protein is also the receptor for HIV, a T-lymphotropic RNA virus responsible for the human acquired immune deficiency syndrome (AIDS) (refs 4-7). To define the mechanisms of interaction of CD4 with the surface of antigen-presenting cells and with HIV, we have isolated the CD4 gene and expressed this gene in several different cellular environments. Here we describe an efficient expression system in which a recombinant, soluble form of CD4 (sCD4) is secreted into tissue culture supernatants. This sCD4 retains the structural and biological properties of CD4 on the cell surface, binds to the envelope glycoprotein (gp110) of HIV and inhibits the binding of virus to CD4+ lymphocytes, resulting in a striking inhibition of virus infectivity.

562 citations

Journal ArticleDOI
TL;DR: The data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis, and several other enveloped viruses including Ebola and Sindbis also useCD209L as a portal of entry.
Abstract: Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450–454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S590 and S1180. Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1–16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis.

562 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20242
20234,275
20228,706
20213,455
20203,848
20193,309