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1.
Emerg Infect Dis ; 23(4): 654-657, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28322698

RESUMO

Sampling of mallards in Alaska during September 2014-April 2015 identified low pathogenic avian influenza A virus (subtypes H5N2 and H1N1) that shared ancestry with highly pathogenic reassortant H5N2 and H5N1 viruses. Molecular dating indicated reassortment soon after interhemispheric movement of H5N8 clade 2.3.4.4, suggesting genetic exchange in Alaska or surrounds before outbreaks.


Assuntos
Surtos de Doenças/veterinária , Patos/virologia , Influenza Aviária/virologia , Vírus Reordenados/genética , Animais , Animais Selvagens , Monitoramento Epidemiológico , Influenza Aviária/epidemiologia
2.
Emerg Microbes Infect ; 5(8): e81, 2016 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-27485496

RESUMO

Influenza A virus (IAV) has been associated with multiple unusual mortality events (UMEs) in North Atlantic pinnipeds, frequently attributed to spillover of virus from wild-bird reservoirs. To determine if endemic infection persists outside of UMEs, we undertook a multiyear investigation of IAV in healthy, live-captured Northwest Atlantic gray seals (Halichoerus grypus). From 2013 to 2015, we sampled 345 pups and 57 adults from Cape Cod, MA, USA and Nova Scotia, Canada consistently detecting IAV infection across all groups. There was an overall viral prevalence of 9.0% (95% confidence interval (CI): 6.4%-12.5%) in weaned pups and 5.3% (CI: 1.2%-14.6%) in adults, with seroprevalences of 19.3% (CI: 15.0%-24.5%) and 50% (CI: 33.7%-66.4%), respectively. Positive sera showed a broad reactivity to diverse influenza subtypes. IAV status did not correlate with measures of animal health nor impact animal movement or foraging. This study demonstrated that Northwest Atlantic gray seals are both permissive to and tolerant of diverse IAV, possibly representing an endemically infected wild reservoir population.


Assuntos
Animais Selvagens/virologia , Reservatórios de Doenças , Vírus da Influenza A/genética , Influenza Humana/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Focas Verdadeiras/virologia , Animais , Anticorpos Antivirais/sangue , Canadá/epidemiologia , Monitoramento Epidemiológico , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/transmissão , Influenza Humana/virologia , Nova Escócia/epidemiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Reação em Cadeia da Polimerase , Prevalência , RNA Viral/sangue , Telemetria , Estados Unidos/epidemiologia
3.
PLoS Pathog ; 9(4): e1003291, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23593001

RESUMO

Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4⁺ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4⁺ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC--T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3--CD169 interaction) for DC-dependent HIV dissemination.


Assuntos
Linfócitos T CD4-Positivos/virologia , Células Dendríticas/virologia , Gangliosídeo G(M3)/metabolismo , HIV-1/fisiologia , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Regulação para Baixo , Gangliosídeo G(M3)/genética , Células HEK293 , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Interferon-alfa/metabolismo , Camundongos , Interferência de RNA , Ratos , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Transdução de Sinais
4.
Adv Exp Med Biol ; 762: 131-53, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22975874

RESUMO

Glycosphingolipids (GSLs) are components of the cell membrane that comprise a membrane bound lipid, ceramide, coupled to an extracellular carbohydrate. GSLs impact numerous aspects of membrane biology, including membrane fluidity, curvature, and organization. The role of these molecules in both chronic inflammation and infectious disease and underlying pathogenic mechanisms are just starting to be recognized. As a component of the cell membrane, GSLs are also incorporated into lipid bilayers of diverse enveloped viruses as they bud out from the host cell and can go on to have a significant influence on viral pathogenesis. Dendritic cell (DC) subsets located in the peripheral mucosal tissues are proposed to be one of the earliest cell types that encounter transmitted viruses and help initiate adaptive immune responses against the invading pathogen by interacting with T cells. In turn, viruses, as obligatory intracellular parasites, rely on host cells for completing their replication cycle, and not surprisingly, HIV has evolved to exploit DC biology for the initial transmission event as well as for its dissemination and propagation within the infected host. In this review, we describe the mechanisms by which GSLs impact DC-mediated HIV trans-infection by either modulating virus infectivity, serving as a direct virus particle-associated host-derived ligand for specific interactions with DCs, or modulating the T cell membrane in such a way as to impact viral entry and thereby productive infection of CD4(+) T cells.


Assuntos
Células Dendríticas/imunologia , Glicoesfingolipídeos/fisiologia , Infecções por HIV/transmissão , HIV-1/fisiologia , Infecções por HIV/imunologia , Humanos
5.
Proc Natl Acad Sci U S A ; 109(19): 7475-80, 2012 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-22529395

RESUMO

The interaction between HIV and dendritic cells (DCs) is an important early event in HIV-1 pathogenesis that leads to efficient viral dissemination. Here we demonstrate a HIV gp120-independent DC capture mechanism that uses virion-incorporated host-derived gangliosides with terminal α2-3-linked sialic acid linkages. Using exogenously enriched virus and artificial liposome particles, we demonstrate that both α2-3 gangliosides GM1 and GM3 are capable of mediating this interaction when present in the particle at high levels. In the absence of overexpression, GM3 is the primary ligand responsible for this capture mechanism, because siRNA depletion of GM3 but not GM1 from the producer cell and hence virions, resulted in a dramatic decrease in DC capture. Furthermore, HIV-1 capture by DCs was competitively inhibited by targeting virion-associated GM3, but was unchanged by targeting GM1. Finally, virions were derived from monocytoid THP-1 cells that constitutively display low levels of GM1 and GM3, or from THP-1 cells induced to express high surface levels of GM1 and GM3 upon stimulation with the TLR2/1 ligand Pam3CSK4. Compared with untreated THP-1 cells, virus produced from Pam3CSK4-stimulated THP-1 cells incorporated higher levels of GM3, but not GM1, and showed enhanced DC capture and trans-infection. Our results identify a unique HIV-1 DC attachment mechanism that is dependent on a host-cell-derived ligand, GM3, and is a unique example of pathogen mimicry of host-cell recognition pathways that drive virus capture and dissemination in vivo.


Assuntos
Células Dendríticas/imunologia , Gangliosídeo G(M3)/imunologia , HIV-1/imunologia , Vírion/imunologia , Linhagem Celular , Células Cultivadas , Células Dendríticas/metabolismo , Células Dendríticas/virologia , Citometria de Fluxo , Gangliosídeo G(M1)/imunologia , Gangliosídeo G(M1)/metabolismo , Gangliosídeo G(M3)/metabolismo , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Gangliosídeo Galactosiltransferase , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Glicoesfingolipídeos/imunologia , Glicoesfingolipídeos/metabolismo , Células HEK293 , HIV-1/fisiologia , Células HeLa , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lipopeptídeos/farmacologia , Lipossomos/imunologia , Lipossomos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/virologia , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/metabolismo , Interferência de RNA , Vírion/metabolismo
6.
J Virol ; 85(11): 5262-74, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21430056

RESUMO

A major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is the design of Envelope (Env)-based immunogens effective at eliciting heterologous or broad neutralizing antibodies (NAbs). We hypothesized that programming the B-cell response could be achieved by sequentially exposing the host to a collection of env variants representing the viral quasispecies members isolated from an individual that developed broad NAbs over time. This ordered vaccine approach (sequential) was compared to exposure to a cocktail of env clones (mixture) and to a single env variant (clonal). The three strategies induced comparable levels of the autologous and heterologous neutralization of tier 1 pseudoviruses. Sequential and mixture exposure to quasispecies led to epitope targeting similar to that observed in the simian-human immunodeficiency virus (SHIV)-infected animal from which the env variants were cloned, while clonal and sequential exposure led to greater antibody maturation than the mixture. Therefore, the sequential vaccine approach best replicated the features of the NAb response observed in that animal. This study is the first to explore the use of a collection of HIV-1 env quasispecies variants as immunogens and to present evidence that it is possible to educate the B-cell response by sequential exposure to native HIV-1 quasispecies env variants derived from an individual with a broadened NAb response.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , Imunização/métodos , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Animais , Ensaio de Imunoadsorção Enzimática , HIV-1/genética , Humanos , Macaca mulatta , Dados de Sequência Molecular , Testes de Neutralização , RNA Viral/genética , Coelhos , Análise de Sequência de DNA , Produtos do Gene env do Vírus da Imunodeficiência Humana/administração & dosagem , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
7.
J Virol ; 83(17): 9002-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19535443

RESUMO

Two frequently employed methods for generating well-characterized, genetically defined infectious human immunodeficiency virus type 1 in vitro include the use of infectious molecular clones (IMCs) and pseudoviruses (PVs) competent for single-round infection. We compared six matched pairs of IMCs and PVs. The relative amounts of Env incorporated and efficiency of cleavage differed substantially between the two systems. Altering the ratio of proviral genome and env expression plasmids can produce pseudovirions that are structurally more similar to the matched IMCs. Differences in Env incorporation and cleavage translated into moderate differences in assays infectivity and sensitivity to neutralizing antibodies and entry inhibitors.


Assuntos
Anticorpos Antivirais/imunologia , Inibidores da Fusão de HIV/farmacologia , HIV-1/crescimento & desenvolvimento , HIV-1/genética , Vírion/química , Produtos do Gene env do Vírus da Imunodeficiência Humana/análise , Linhagem Celular , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos
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