The mechanism of cross-protection afforded by dengue virus against West Nile virus in hamsters

Price, Winston H.; Thind, Inderjit S.

doi:10.1017/s0022172400022476

Cited by 22 publications

(13 citation statements)

References 5 publications

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“…Studies from several decades ago showed that polyclonal sera directed against the E protein can protect against lethal flavivirus challenge in animals (6,41). More recent experiments with WNV, DENV-1, and DENV-2 (4,15,16,37,46,49,53) have suggested that DIII of the E protein is a key target for strongly neutralizing MAbs, although the human B cell repertoire may be directed away from this region (38,55,59).…”

Section: Generation Of Mabsmentioning

confidence: 99%

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Brien

Austin

Sukupolvi-Petty

et al. 2010

J Virol

134

148

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Dengue viruses (DENV) comprise a family of related positive-strand RNA viruses that infect up to 100 million people annually. Currently, there is no approved vaccine or therapy to prevent infection or diminish disease severity. Protection against DENV is associated with the development of neutralizing antibodies that recognize the viral envelope (E) protein. Here, with the goal of identifying monoclonal antibodies (MAbs) that can function as postexposure therapy, we generated a panel of 82 new MAbs against DENV-3, including 24 highly neutralizing MAbs. Using yeast surface display, we localized the epitopes of the most strongly neutralizing MAbs to the lateral ridge of domain III (DIII) of the DENV type 3 (DENV-3) E protein. While several MAbs functioned prophylactically to prevent DENV-3-induced lethality in a stringent intracranial-challenge model of mice, only three MAbs exhibited therapeutic activity against a homologous strain when administered 2 days after infection. Remarkably, no MAb in our panel protected prophylactically against challenge by a strain from a heterologous DENV-3 genotype. Consistent with this, no single MAb neutralized efficiently the nine different DENV-3 strains used in this study, likely because of the sequence variation in DIII within and between genotypes. Our studies suggest that strain diversity may limit the efficacy of MAb therapy or tetravalent vaccines against DENV, as neutralization potency generally correlated with a narrowed genotype specificity.Dengue viruses (DENV) cause the most common arthropod-borne viral infection in humans worldwide, with ϳ50 million to 100 million people infected annually and ϳ2.5 billion people at risk (13, 61). Infection by four closely related but serologically distinct viruses of the Flavivirus genus (DENV serotypes 1, 2, 3, and 4 [DENV-1 to -4, respectively]) cause dengue fever (DF), an acute, self-limiting, yet severe, febrile illness, or dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), a potentially fatal syndrome characterized by vascular leakage and a bleeding diathesis. Specific treatment or prevention of dengue disease is supportive, as there is no approved antiviral therapy or vaccine available.DENV has an ϳ11-kb, single-stranded, positive-sense RNA genome that is translated into a polyprotein and is cleaved posttranslationally into three structural (envelope [E], pre/ membrane [prM], and capsid [C]) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. The three structural proteins encapsidate a single infectious RNA of the DENV genome, whereas the nonstructural proteins have key enzymatic or regulatory functions that promote replication. Additionally, several DENV proteins are multifunctional and modulate cell-intrinsic and cell-extrinsic host immune responses (10).Most flavivirus-neutralizing antibodies recognize the structural E protein (reviewed in reference 40). Based on X-ray crystallographic analysis (32, 33), the DENV E protein is divided into three domains: domain I (DI), which is an 8-strand...

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Section: Generation Of Mabsmentioning

confidence: 99%

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Brien

Austin

Sukupolvi-Petty

et al. 2010

J Virol

134

148

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“…Enhanced infection after transfer of either pooled human cord blood from DENV-immune mothers (Halstead, 1979) or a chimeric human-chimpanzee anti-DENV neutralizing monoclonal antibody (mAb) (Goncalvez et al, 2007) resulted in increased viremia in rhesus monkeys that is postulated to represent antibody-dependent enhancement (ADE). In mice, protection from death using a secondary, homologous (serotype-specific) DENV infection has been demonstrated (Johnson and Roehrig, 1999; Price and Thind, 1972); while reports of heterologous sequential DENV infections in mice noted an increase in thrombocytopenia (Sarkar et al, 1976) or documented heterologous immune responses (Beaumier et al, 2008). To the best of our knowledge, no published study in mice has documented the occurrence of either protection or enhancement of DENV titers in sequential, heterologous infections.…”

Section: Introductionmentioning

confidence: 99%

Antibodies play a greater role than immune cells in heterologous protection against secondary dengue virus infection in a mouse model

Kyle¹,

Balsitis²,

Zhang³

et al. 2008

Virology

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The four serotypes of dengue virus (DENV1-4) are causative agents of dengue fever and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Previous DENV infection is a risk factor for DHF/DSS during subsequent infection by a different serotype. Nonetheless, most primary and secondary DENV infections are asymptomatic. To investigate the possible mechanisms of immune protection in vivo, 129/Pas mice lacking IFN-α/β and -γ receptors (AG129) were used to model secondary infection using both DENV1-DENV2 and DENV2-DENV4 sequences. At intervals between sequential infections of 4 to 52 weeks, protection against secondary heterologous DENV infection was observed. Passive transfer of DENV-immune serum was protective against replication of heterologous challenge virus in all tissues tested, whereas adoptive transfer of DENV-immune cells significantly protected mice from replication of the challenge virus only when a lower inoculum was administered. These findings are relevant for understanding both natural and vaccine-induced immunity to DENV.

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“…WNV infection has been studied in several animal models, including chickens, geese, rat, mice, hamsters, and monkeys (4,9,17,31,41,48). However, the pathophysiology of invasiveness of WNV into the CNS, the mechanism of neurodegeneration, and the immune response after infection are still poorly understood.…”

mentioning

confidence: 99%

CD8⁺T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

Wang

Lobigs

Lee

et al. 2003

J Virol

255

204

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The mechanism of cross-protection afforded by dengue virus against West Nile virus in hamsters

Cited by 22 publications

References 5 publications

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Antibodies play a greater role than immune cells in heterologous protection against secondary dengue virus infection in a mouse model

CD8⁺T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

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The mechanism of cross-protection afforded by dengue virus against West Nile virus in hamsters

Cited by 22 publications

References 5 publications

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Antibodies play a greater role than immune cells in heterologous protection against secondary dengue virus infection in a mouse model

CD8+T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

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Product

Resources

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CD8⁺T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis