Relative contribution of nonstructural protein 1 in dengue pathogenesis

Lee, Pei Xuan; Ting, Donald Heng Rong; Boey, Clement Peng Hee; Tan, Eunice Tze Xin; Chia, Janice Zuo Hui; Idris, Fakhriedzwan; Oo, Yukei; Ong, Li Ching; Chua, Yen Leong; Hapuarachchi, Chanditha; Ng, Lee Ching; Alonso, Sylvie

doi:10.1084/jem.20191548

Cited by 25 publications

(34 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent studies using non-mouse adapted, mouse-virulent DENV2 strains (D2Y98P and EHIE2862Y15) found that secreted NS1 did not have a strong pathogenic role, nor did NS1 immunity confer protection in interferon αβ receptor knockout (A129) and interferon αβγ receptor knockout (AG129) mice. This is hypothesized to occur because the virulence of these strains relies on their structural components [41]. It is suggested that the role of NS1 in pathogenesis is strain-dependent, so NS1 may not be well suited as the universal vaccine immunogen for DENV.…”

Section: Role Of Ns1 In Dengue Pathogenesismentioning

confidence: 99%

Flavivirus NS1 and Its Potential in Vaccine Development

Carpio

Barrett

2021

Vaccines

View full text Add to dashboard Cite

The Flavivirus genus contains many important human pathogens, including dengue, Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), yellow fever (YF) and Zika (ZIK) viruses. While there are effective vaccines for a few flavivirus diseases (JE, TBE and YF), the majority do not have vaccines, including WN and ZIK. The flavivirus nonstructural 1 (NS1) protein has an unusual structure–function because it is glycosylated and forms different structures to facilitate different roles intracellularly and extracellularly, including roles in the replication complex, assisting in virus assembly, and complement antagonism. It also plays a role in protective immunity through antibody-mediated cellular cytotoxicity, and anti-NS1 antibodies elicit passive protection in animal models against a virus challenge. Historically, NS1 has been used as a diagnostic marker for the flavivirus infection due to its complement fixing properties and specificity. Its role in disease pathogenesis, and the strong humoral immune response resulting from infection, makes NS1 an excellent target for inclusion in candidate flavivirus vaccines.

show abstract

Section: Role Of Ns1 In Dengue Pathogenesismentioning

confidence: 99%

Flavivirus NS1 and Its Potential in Vaccine Development

Carpio

Barrett

2021

Vaccines

View full text Add to dashboard Cite

show abstract

“…The presence of NS1 antibodies correlates with lower disease severity in dengue patients [5,27], and robust protection against DENVinduced hemorrhage, coagulopathy, viremia, and mortality [27,28]. However, the development of anti-NS1 therapies to weaken DENV severity has recently been challenged, as researchers found that the pathogenic role of NS1 is DENV strain dependent [29], and the potency of DENV NS1 to permeate the NVU has been shown to be much less effective than the NS1 protein of another Flaviviridae member WNV [30]. WNV being a 'true' neurotropic virus, one could envision to use anti-WNV NS1 antibodies to treat WNV-induced encephalitis.…”

Section: Trends In Molecular Medicinementioning

confidence: 99%

Targeting tight junctions to fight against viral neuroinvasion

Gaudin

Brychka

Sips

et al. 2022

Trends in Molecular Medicine

View full text Add to dashboard Cite

The clinical impact of viral neuroinvasion on the central nervous system (CNS) ranges from barely detectable to deadly, including acute and chronic outcomes. Developing innovative therapeutic strategies is important to mitigate virusinduced neurological and psychiatric disorders. A key gatekeeper to the CNS is the neurovascular unit (NVU), a major obstacle to viral neuroinvasion and antiviral therapies. The NVU isolates the brain from the blood through firm sealing operated by the tight junctions (TJs) of endothelial cells. Here, we make the thoughtprovoking assumption that TJs can be targets to prevent or treat viral neuroinvasion and resulting disorders. This review aims at defining the conceptual diverse mode of actions of such approaches, evaluates their feasibility, and discusses future challenges in the field. Tight junctions of the neurovascular unit: a ticket to the central nervous systemInfectious diseases that affect the central nervous system (CNS; see Glossary) are commonly observed in clinical practice [1]. Neurotropic viral infection can cause acute or chronic syndromes, including encephalitis, meningitis, meningoencephalomyelitis, Guillain-Barré-like-syndromes, or stroke. In the case of virus induced encephalitis, the incidence ranges from 1.5 to 7 cases/100 000 inhabitants/year, excluding epidemics [2]. This condition is severe, with high mortality rates, as exemplified by a Danish study estimating the cumulative mortality rate of patients with herpes simplex encephalitis at 18.6% [3]. In the United States for instance, encephalitis hospitalizations result in 5.6% mortality, among which infectious agents account for about 40% of deaths [4]. These studies highlight the importance of finding potent cures to fight neurotropic viral infections.

show abstract

“…Although the LP is an effective mechanism to limit infection, DENV has developed strategies to protect itself from a lectin-mediated attack ( Table 1 and Figure 2 B). DENV produces a nonstructural protein (NS1) to assist in intracellular viral replication [ 98 , 99 ], enhance dengue infection [ 100 , 101 , 102 ] and modulate the endothelial hyperpermeability, potentially to disseminate infections [ 103 , 104 , 105 , 106 ], which could further contribute to dengue pathogenesis [ 99 , 107 ]. NS1 is a glycoprotein that can be detected as intracellular, surface membrane-associated and secreted forms [ 45 , 99 ].…”

Section: Lectin Pathway In Denguementioning

confidence: 99%

Dengue and the Lectin Pathway of the Complement System

Kraivong

Punyadee

Liszewski

et al. 2021

Viruses

View full text Add to dashboard Cite

Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system’s lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern recognition receptor (PRR) binding efficiency. The important PRR, mannan binding lectin (MBL), mediates DENV neutralization through (1) a complement activation-independent mechanism via direct MBL glycan recognition, thereby inhibiting DENV attachment to host target cells, or (2) a complement activation-dependent mechanism following the attachment of complement opsonins C3b and C4b to virion surfaces. The serum concentrations of lectin PRRs and their polymorphisms influence these LP activities. Conversely, to escape the LP attack and enhance the infectivity, DENV utilizes the secreted form of nonstructural protein 1 (sNS1) to counteract the MBL effects, thereby increasing viral survival and dissemination.

show abstract

Relative contribution of nonstructural protein 1 in dengue pathogenesis

Cited by 25 publications

References 72 publications

Flavivirus NS1 and Its Potential in Vaccine Development

Flavivirus NS1 and Its Potential in Vaccine Development

Targeting tight junctions to fight against viral neuroinvasion

Dengue and the Lectin Pathway of the Complement System

Contact Info

Product

Resources

About