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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: The first glimpse of the total human T cell response to a complex infectious agent is provided and insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans is provided.
Abstract: Human cytomegalovirus (HCMV) infections of immunocompetent hosts are characterized by a dynamic, life-long interaction in which host immune responses, particularly of T cells, restrain viral replication and prevent disease but do not eliminate the virus or preclude transmission. Because HCMV is among the largest and most complex of known viruses, the T cell resources committed to maintaining this balance have never been characterized completely. Here, using cytokine flow cytometry and 13,687 overlapping 15mer peptides comprising 213 HCMV open reading frames (ORFs), we found that 151 HCMV ORFs were immunogenic for CD4 + and/or CD8 + T cells, and that ORF immunogenicity was influenced only modestly by ORF expression kinetics and function. We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average ∼10% of both the CD4 + and CD8 + memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8 + T cells and was rare. These data provide the first glimpse of the total human T cell response to a complex infectious agent and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.

1,272 citations

Journal ArticleDOI
07 Sep 2001-Science
TL;DR: Using reverse genetics, it is shown that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice, and high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.
Abstract: In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.

1,267 citations

Journal ArticleDOI
28 Apr 2005-Nature
TL;DR: The data demonstrate that over one-half of all memory CD4+ T cells in SIV-infected macaques are destroyed directly by viral infection during the acute phase—an insult that certainly heralds subsequent immunodeficiency.
Abstract: It has recently been established that both acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are accompanied by a dramatic and selective loss of memory CD4+ T cells predominantly from the mucosal surfaces. The mechanism underlying this depletion of memory CD4+ T cells (that is, T-helper cells specific to previously encountered pathogens) has not been defined. Using highly sensitive, quantitative polymerase chain reaction together with precise sorting of different subsets of CD4+ T cells in various tissues, we show that this loss is explained by a massive infection of memory CD4+ T cells by the virus. Specifically, 30-60% of CD4+ memory T cells throughout the body are infected by SIV at the peak of infection, and most of these infected cells disappear within four days. Furthermore, our data demonstrate that the depletion of memory CD4+ T cells occurs to a similar extent in all tissues. As a consequence, over one-half of all memory CD4+ T cells in SIV-infected macaques are destroyed directly by viral infection during the acute phase-an insult that certainly heralds subsequent immunodeficiency. Our findings point to the importance of reducing the cell-associated viral load during acute infection through therapeutic or vaccination strategies.

1,260 citations

Journal ArticleDOI
TL;DR: Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations.
Abstract: A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0–39 months) autologous viruses, whereas responses to laboratory and heterologous primary strains were often lower and delayed. Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.

1,257 citations

Journal ArticleDOI
21 Jun 2012-Nature
TL;DR: Results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolate, which will inform the development, production and distribution of effective countermeasures.
Abstract: Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to hostspecific cellular receptors 1–3 . Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus—comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus—that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian–human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to

1,255 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