Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells

Silva, Maria Carlan; Guerrero-Plata, Antonieta; Gilfoy, Felicia D.; Garofalo, Roberto P.; Mason, Peter W.

doi:10.1128/jvi.00857-07

Cited by 87 publications

(97 citation statements)

References 70 publications

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“…Similarly, mosquito cell-derived WNV or envelope protein, which displays N-linked carbohydrates in a high mannose form, inhibited the poly(I-C)-induced production of TNF-␣ and IFN-␣/␤, whereas Vero cell-derived WNV, which displays complex processed sugars, did not (4). Analogously, Vero but not insect cell-derived WNV induced IFN-␣ and the inflammatory chemokine CXCL10 in plasmacytoid dendritic cells (52). Cell-specific differences in infectious particle-to-antigen ratios or the content of RNA-containing defective viral particles also could independently affect the induction of innate immune responses.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection

Daffis¹,

Samuel

Suthar

et al. 2008

J Virol

308

291

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Protection against West Nile virus (WNV) infection requires rapid viralRecent studies have begun to delineate the molecular mechanisms that regulate alpha interferon (IFN-␣) and IFN-␤ induction after infection by RNA and DNA viruses (reviewed in references 13, 24, 25, and 57). Pattern recognition receptors (PRR) sense conserved structural microbial elements identified as pathogen-associated molecular patterns. PRR involved in the recognition of RNA viruses can be divided into two classes. Toll-like receptors (TLR) on the cell surface or within endosomes recognize single-and double-stranded RNA and signal through the adaptor molecules MyD88 and TRIF. In comparison, RIG-I and MDA5 helicases recognize single-and double-stranded RNA in the cytosol and signal through the adaptor protein IPS-1 (also known as MAVS, Cardif, and VISA) (reviewed in references 28, 42, and 55). Recognition by viral RNA sensors results in the downstream activation and nuclear translocation of IRF-3 and IRF-7, which transcriptionally activate IFN-␣ and -␤ gene promoters (46).Cell culture experiments defined TLR3 as a PRR that recognizes double-stranded RNA, activates IRF-3 and NF-B transcriptional pathways, and induces type I IFN (2). The role of TLR3 in vivo in protection against viral infections has been less clear (reviewed in references 5, 36, and 58). Experiments in TLR3Ϫ/Ϫ mice infected with lymphocytic choriomeningitis virus, vesicular stomatitis virus, and reovirus failed to show increased mortality or altered viral burden phenotypes (12). In contrast, TLR3 restricts replication, regulates cytokine production, and protects against infection by mouse cytomegalovirus and encephalomyocarditis virus (EMCV) (21, 54). Indeed, a deficiency in TLR3 in humans was identified as a predisposing genetic risk factor for herpes simplex virus (HSV) encephalitis (61) and influenza A virus-induced encephalopathy (23). An adverse role for TLR3 also has been proposed since TLR3 Ϫ/Ϫ mice infected with influenza, punta toro, and vaccinia viruses showed improved survival and decreased production of inflammatory cytokines (19,26,33). Analogously, conflicting results have been observed with respect to the role of TLR3 in inducing IFN after infection with the encephalitic flavivirus West Nile virus (WNV). TLR3 was largely dispensable for WNV recognition and induction of IFN responses in vitro (15, 47), whereas in mice, an absence of TLR3 protected mice from lethal infection (59). TLR3 Ϫ/Ϫ mice infected via intraperitoneal injection with WNV showed decreased systemic tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6) production, blood-brain barrier (BBB) permeability, and infection in the brain.Given this apparent conflict and our previous studies demonstration of an essential role for IRF-3 in controlling WNV infection (6), we reexamined the pathogenesis of virulent WNV infection in TLR3 Ϫ/Ϫ mice. Remarkably, we observed increased susceptibility of TLR3 Ϫ/Ϫ mice to WNV infection. TLR3 had a modest effect on WNV infection in peripheral tissues and was...

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Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection

Daffis¹,

Samuel

Suthar

et al. 2008

J Virol

308

291

View full text Add to dashboard Cite

show abstract

“…Our results demonstrated that this phenomenon cannot be generalized to DENV as both mosquito and mammalian cell-derived viruses had incompletely processed, high-mannose glycans and were able to infect DC-SIGN-bearing cells efficiently. In studies with alphaviruses and WNV, the superior infectivity of mosquito cell-derived virus has also been attributed to the ability of mosquito cell-but not mammalian cell-grown virus to suppress type I interferon responses (Shabman et al, 2007;Silva et al, 2007). The mechanism by which mosquito cell-derived virus suppresses this innate immune response is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

N-Linked glycans on dengue viruses grown in mammalian and insect cells

Hacker

White

Silva

2009

Journal of General Virology

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This study compared the ability of mosquito and mammalian cell-derived dengue virus (DENV) to infect human dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)-expressing cells and characterized the structure of envelope (E) protein N-linked glycans on DENV derived from the two cell types. DENVs derived from both cell types were equally effective at infecting DC-SIGN-expressing human monocytes and dendritic cells. The N-linked glycans on mosquito cellderived virus were a mix of high-mannose and paucimannose glycans. In virus derived from mammalian cells, the N-linked glycans were a mix of high-mannose and complex glycans. These results indicate that N-linked glycans are incompletely processed during DENV egress from cells, resulting in high-mannose glycans on viruses derived from both cell types. Studies with full-length and truncated E protein demonstrated that incomplete processing was most likely a result of the poor accessibility of glycans on the membrane-anchored protein. INTRODUCTIONDengue viruses (DENVs) are enveloped, positive-sense RNA viruses of the genus Flavivirus that are transmitted via the bite of Aedes mosquitoes. Each year, over 2.5 billion people are at risk of contracting dengue, 100 million people develop symptomatic infections and up to 2.5 % of dengue haemorrhagic fever (DHF) patients die (Gubler, 2002;Gubler & Clark, 1995; WHO, 2009). Despite the public health importance of dengue, the cell biology of DENV is poorly understood. Vector-borne viruses such as DENV must productively infect cells of both arthropod and mammalian origin. As the posttranslational protein-processing machinery is different in insect and mammalian cells, the structure of glycoproteins produced in the two hosts may be different. Recent work with a wide variety of viruses has shown that protein glycosylation can influence viral virulence (reviewed by Vigerust & Shepherd, 2007). Recent studies with alphaviruses, which are also transmitted by arthropod vectors, have demonstrated that membraneprotein N-linked oligosaccharides are differentially processed by enzymes in insect and mammalian cells (Shabman et al., 2008). Structural differences in the glycans derived from insect and mammalian cells influence the ability of the viruses to infect target cells (Klimstra et al., 2003;Shabman et al., 2007Shabman et al., , 2008. In this study, we characterized the N-linked glycans on the envelope protein of DENVs grown in different cell types and assessed the functional consequences of these differences.The DENV particle is made up of three structural proteins: envelope (E), membrane (M) and capsid (C) (Chambers et al., 1990b;Kuhn et al., 2002). The E protein is the major membrane glycoprotein on the surface of the virion, responsible for virus attachment and fusion (Chambers et al., 1990b). Human dendritic cells (DCs) are a target of DENV infection (Ho et al., 2001;Marovich et al., 2001;Wu et al., 2000). Infection of DCs is mediated by the binding of DENV to DC-specific ICAM3-grabbing non-integrin (DC-SIGN), a C-type lec...

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“…Extrinsic antiviral activity is defined as the ability of macrophages to influence extracellular virus and to interfere with virus replication in surrounding permissive cells. Also it is marked, that during the development of some virus infections the activated macrophage gets an ability to distinguish infected and intact cells (Silva et al, 2007). Thus, the value of monocytes/macrophages in virus infections is defined by their functional condition.…”

Section: The Monocytes/macrophages In Tick-borne Encephalitismentioning

confidence: 99%