Flavivirus NS1: a multifaceted enigmatic viral protein

Rastogi, Meghana; Sharma, Nikhil; Singh, Sunit K.

doi:10.1186/s12985-016-0590-7

Cited by 230 publications

(187 citation statements)

References 94 publications

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“…Despite its high specificity (6,11), the study performed here underscores the limitations of the current Zika NS1-based ELISA. Therefore, other serological diagnosis tests that would increase the sensitivity of Zika antibody detection should be developed.…”

Section: Discussionmentioning

confidence: 97%

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile

et al. 2017

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Serological diagnosis of Zika virus is challenging due to high crossreactivity of Zika virus with other flavivirus antibodies. Recently, a Zika NS1-based enzyme-linked immunosorbent assay (ELISA) was developed and shown to be highly specific for Zika antibody detection; however, sensitivity was evaluated for only a small number of confirmed Zika-infected patients. In this study, we measured the sensitivity and kinetics of Zika IgM and IgG antibodies using the Zika NS1-based ELISA in 105 samples from 63 returning travelers infected with Zika virus (proven by PCR or neutralization assay) from Israel, Czech Republic, Italy, Belgium, Germany, and Chile. Zika virus IgM was detected from 2 to 42 days post-symptom onset (PSO) with an overall sensitivity of 79% in the first month and 68% until 2 months PSO, while IgG antibodies were detected from 5 days to 3 years PSO with 79% sensitivity. Interestingly, significant differences in IgM sensitivity and IgM detection period were observed between Israeli and European/Chilean Zika-infected travelers, adding to the complexity of Zika infection diagnosis and suggesting that other diagnostic methods should be complemented to reduce false-negative results.

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Section: Discussionmentioning

confidence: 97%

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile

et al. 2017

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“…The E protein of WNV hinders ubiquitination of RIP-1 to inhibit RIG-I-mediated and TLR3-dependent antiviral pathways [62]. The NS2A, NS4A and NS4B proteins of DENV reduce phosphorylation and nuclear translocation of signal transducer and activator of transcription 1, ultimately suppressing IFN signalling [63,64]. However, there are only a few reports to date regarding the role of NS1 in interfering with the innate immune response.…”

Section: The Innate Immune Response To Avian Tmuv Infectionmentioning

confidence: 99%

An updated review of avian-origin Tembusu virus: a newly emerging avian Flavivirus

Zhang

Chen

Mahalingam

et al. 2017

Journal of General Virology

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Tembusu virus (TMUV, genus Flavivirus, family Flaviviridae) was first isolated in 1955 from Culex tritaeniorhynchus mosquitoes in Kuala Lumpur, Malaysia. In April 2010, duck TMUV was first identified as the causative agent of egg-drop syndrome, characterized by a substantial decrease in egg laying and depression, growth retardation and neurological signs or death in infected egg-laying and breeder ducks, in the People's Republic of China. Since 2010, duck TMUV has spread to most of the duck-producing regions in China, including many of the coastal provinces, neighbouring regions and certain Southeast Asia areas (i.e. Thailand and Malaysia). This review describes the current understanding of the genome characteristics, host range, transmission, epidemiology, phylogenetic and immune evasion of avian-origin TMUV and the innate immune response of the host.

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“…Antibodies targeting the ZIKV NS1 protein were shown previously to induce protective Fc-mediated effector functions by an in vitro reporter assay (21). This is likely due to the high abundance of NS1 expressed at the surface of virally infected cells (36). In contrast, the ZIKV envelope protein is less accessible at the cell surface as ZIKV particles bud internally from the Golgi apparatus rather than from the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein

Bailey

Broecker

Freyn

et al. 2019

J Virol

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The mosquito-borne Zika virus (ZIKV) has been causing epidemic outbreaks on a global scale. Virus infection can result in severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we characterized monoclonal antibodies isolated from a patient with an active Zika virus infection that potently neutralized virus infection in Vero cells at the nanogram-per-milliliter range. In addition, these antibodies enhanced internalization of virions into human leukemia K562 cells in vitro, indicating their possible ability to cause antibody-dependent enhancement of disease. Escape variants of the ZIKV MR766 strain to a potently neutralizing antibody, AC10, exhibited an amino acid substitution at residue S368 in the lateral ridge region of the envelope protein. Analysis of publicly availably ZIKV sequences revealed the S368 site to be conserved among the vast majority (97.6%) of circulating strains. We validated the importance of this residue by engineering a recombinant virus with an S368R point mutation that was unable to be fully neutralized by AC10. Four out of the 12 monoclonal antibodies tested were also unable to neutralize the virus with the S368R mutation, suggesting this region to be an important immunogenic epitope during human infection. Last, a time-of-addition infection assay further validated the escape variant and showed that all monoclonal antibodies inhibited virus binding to the cell surface. Thus, the present study demonstrates that the lateral ridge region of the envelope protein is likely an immunodominant, neutralizing epitope. IMPORTANCE Zika virus (ZIKV) is a global health threat causing severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we analyzed the human monoclonal antibody response to acute ZIKV infection and found that neutralizing antibodies could not elicit Fc-mediated immune effector functions but could potentiate antibody-dependent enhancement of disease. We further identified critical epitopes involved with neutralization by generating and characterizing escape variants by whole-genome sequencing. We demonstrate that the lateral ridge region, particularly the S368 amino acid site, is critical for neutralization by domain IIIspecific antibodies.Z ika virus (ZIKV) is a mosquito-borne flavivirus causing epidemic outbreaks on a global scale. Infection with ZIKV is frequently asymptomatic, and clinical manifestations, including low-grade fever, rash, and arthralgia, occur in approximately 20% of

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Flavivirus NS1: a multifaceted enigmatic viral protein

Cited by 230 publications

References 94 publications

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile

An updated review of avian-origin Tembusu virus: a newly emerging avian Flavivirus

Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein

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