Structure of nonstructural protein 1 of dengue and Zika virus: Difference and implication for pathogenesis and vaccine development

2017 ◽  
Vol 10 (4) ◽  
pp. 1074
Author(s):  
Beuy Joob ◽  
Viroj Wiwanitkit
Keyword(s):  
Zika Virus ◽  
Vaccine Development ◽  
Nonstructural Protein ◽  
Nonstructural Protein 1

scholarly journals Attenuation of Zika Virus by Passage in Human HeLa Cells

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 93 ◽  
Author(s):  
Li ◽  
Collins ◽  
Widen ◽  
Davis ◽  
Kaiser ◽  
...  
Keyword(s):  
Hela Cell ◽  
Hela Cells ◽  
Zika Virus ◽  
Infected Animal ◽  
Vaccine Development ◽  
Nonstructural Protein ◽  
A549 Cells ◽  
Wild Type ◽  
Nonstructural Protein 1

Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells.  Therefore, it was hypothesized that wild-type ZIKV would also be attenuated after HeLa cell passaging. A human isolate from the recent ZIKV epidemic was subjected to serial HeLa cell passaging, resulting in attenuated in vitro replication in both Vero and A549 cells. Additionally, infection of AG129 mice with 10 plaque forming units (pfu) of wild-type ZIKV led to viremia and mortality at 12 days, whereas infection with 103 pfu of HeLa-passage 6 (P6) ZIKV led to lower viremia, significant delay in mortality (median survival: 23 days), and increased cytokine and chemokine responses.  Genomic sequencing of HeLa-passaged virus identified two amino acid substitutions as early as HeLa-P3: pre-membrane E87K and nonstructural protein 1 R103K. Furthermore, both substitutions were present in virus harvested from HeLa-P6-infected animal tissue. Together, these data show that, similarly to other mosquito-borne flaviviruses, ZIKV is attenuated following passaging in HeLa cells. This strategy can be used to improve understanding of substitutions that contribute to attenuation of ZIKV and be applied to vaccine development across multiple platforms.

scholarly journals Vesicular Stomatitis Virus and DNA Vaccines Expressing Zika Virus Nonstructural Protein 1 Induce Substantial but Not Sterilizing Protection against Zika Virus Infection

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Anzhong Li ◽  
Miaoge Xue ◽  
Zayed Attia ◽  
Jingyou Yu ◽  
Mijia Lu ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Nonstructural Protein ◽  
Ns1 Protein ◽  
Zikv Infection ◽  
Partial Protection ◽  
Nonstructural Protein 1 ◽  
Vesicular Stomatitis

ABSTRACT The nonstructural protein 1 (NS1) of several flaviviruses, including West Nile, dengue, and yellow fever viruses, is capable of inducing variable degrees of protection against flavivirus infection in animal models. However, the immunogenicity of NS1 protein of Zika virus (ZIKV) is less understood. Here, we determined the efficacy of ZIKV NS1-based vaccine candidates using two delivery platforms, methyltransferase-defective recombinant vesicular stomatitis virus (mtdVSV) and a DNA vaccine. We first show that expression of ZIKV NS1 could be significantly enhanced by optimizing the signal peptide. A single dose of mtdVSV-NS1-based vaccine or two doses of DNA vaccine induced high levels of NS1-specfic antibody and T cell immune responses but provided only partial protection against ZIKV viremia in BALB/c mice. In Ifnar1−/− mice, neither NS1-based vaccine provided protection against a lethal high dose (105 PFU) ZIKV challenge, but mtdVSV-NS1-based vaccine prevented deaths from a low dose (103 PFU) challenge, though they experienced viremia and body weight loss. We conclude that ZIKV NS1 alone conferred substantial, but not complete, protection against ZIKV infection. Nevertheless, these results highlight the value of ZIKV NS1 for vaccine development. IMPORTANCE Most Zika virus (ZIKV) vaccine research has focused on the E or prM-E proteins and the induction of high levels of neutralizing antibodies. However, these ZIKV neutralizing antibodies cross-react with other flaviviruses, which may aggravate the disease via an antibody-dependent enhancement (ADE) mechanism. ZIKV NS1 protein may be an alternative antigen for vaccine development, since antibodies to NS1 do not bind to the virion, thereby eliminating the risk of ADE. Here, we show that recombinant VSV and DNA vaccines expressing NS1, alone, confer partial protection against ZIKV infection in both immunocompetent and immunodeficient mice, highlighting the value of NS1 as a potential vaccine candidate.

Serological Differences after Acute Zika Virus Infections between Children and Adults: Implication for Use of a Serological Test

2021 ◽  
Author(s):  
Jurai Wongsawat ◽  
Patama Suttha ◽  
Sumalee Chanama ◽  
Somkid Srisopa ◽  
Nichapa Yonchoho ◽  
...  
Keyword(s):  
Zika Virus ◽  
Nonstructural Protein ◽  
Serological Test ◽  
Cross Reactivity ◽  
Virus Infections ◽  
Positive Real ◽  
Nonstructural Protein 1 ◽  
Age Related ◽  
Polymerase Chain ◽  
Post Onset

Information is limited regarding differential serological responses after acute Zika virus (ZIKV) infections and prevalence of cross-reactivity with anti-dengue virus (DENV) assays comparing children and adults. Early convalescent sera from a cohort of suspected mild DENV cases between December 2016 and September 2018 at Bamrasnaradura Infectious Diseases Institute in Thailand were tested for nonstructural protein 1 (NS1)–based anti-ZIKV IgM and IgG ELISAs (Euroimmun), and in-house anti-DENV IgM- and IgG-capture ELISAs. ZIKV cases were identified by positive real-time reverse transcriptase-polymerase chain reaction on urine. Sera from 26 (10 children and 16 adults) ZIKV and 237 (153 children and 74 adults) non-ZIKA cases collected at the median duration of 18 days (interquartile range [IQR] 18,19) post-onset of symptoms were tested. Comparing pediatric ZIKV to adult ZIKV cases, the mean anti-ZIKV IgM ratio was higher (2.12 versus 1.27 units, respectively; P = 0.07), whereas mean anti-ZIKV IgG ratio was lower (3.13 versus 4.24 units, respectively; P = 0.03). Sensitivity of anti-ZIKV IgM and specificity of anti-ZIKV IgG in pediatric ZIKV were higher than in adult ZIKV cases (80.0% versus 43.7% and 79.1% versus 43.2%, respectively). No cross-reactivity with anti-DENV IgM- and IgG-capture ELISA were reported in pediatric ZIKV cases in our study, whereas 25% and 12.5% were found in adult ZIKV cases, respectively. Age-related ZIKV serological differences have been observed. Positive NS1-based anti-ZIKV IgM and IgG ELISA at the early convalescent phase could be useful for ZIKV diagnosis in children, even in a dengue endemic setting.

Nanovaccine based on self-assembling nonstructural protein 1 boosts antibody responses to Zika virus

2021 ◽  
Vol 32 ◽  
pp. 102334
Author(s):  
Marianna Teixeira Pinho Favaro ◽  
Monica Josiane Rodrigues-Jesus ◽  
Alexia Adrianne Venceslau-Carvalho ◽  
Rúbens Prince Dos Santos Alves ◽  
Lennon Ramos Pereira ◽  
...  
Keyword(s):  
Zika Virus ◽  
Nonstructural Protein ◽  
Antibody Responses ◽  
Self Assembling ◽  
Nonstructural Protein 1

scholarly journals T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

2018 ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Carlos Brites ◽  
Estela Luz ◽  
Celia Pedroso ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Vaccine Development ◽  
Nonstructural Protein ◽  
Sequence Similarity ◽  
T Cell Responses ◽  
T Cell Response ◽  
Endemic Region ◽  
Cell Responses ◽  
Nonstructural Protein 1

ABSTRACTThe 2015-16 Zika virus (ZIKV) epidemic in the Americas and the Caribbean demonstrates that clinical assays to detect, distinguish, and characterize immune responses to flaviviral infections are needed. ZIKV and dengue virus (DENV) are mosquito-transmitted flaviviruses sharing overlapping geographical distribution and have significant sequence similarity that can increase the potential for antibody and T cell cross-reaction. Using nonstructural protein 1-based enzyme-linked immunosorbent assays (ELISAs), we determine the serostatus of individuals living in a DENV- and ZIKV-endemic region in Brazil, identifying individuals with primary DENV (pDENV) and ZIKV (pZIKV), ZIKV with primary DENV (ZIKVwpDENV), and secondary DENV (sDENV) infections; pDENV and pZIKV were further confirmed by neutralization tests. Development of an enzyme-linked immunospot (ELISPOT) assay for DENV and ZIKV structural and nonstructural (NS) protein antigens enables us to distinguish infections by these viruses based on T cells and to characterize those responses. We find that IFN-γ and TNF-α T cell responses to NS3 differentiates DENV and ZIKV infections with 94% sensitivity and 92% specificity. In general, we also show that pDENV and sDENV cases and pZIKV and ZIKVwpDENV cases elicit similar T cell response patterns, and that HIV-infected individuals have T cell responses that are lower in magnitude compared to HIV-negative individuals. These results have important implications for DENV and ZIKV diagnostic and vaccine development and provide critical insights into the T cell response in individuals with multiple flaviviral infections.

scholarly journals Coronavirus Nsp1: Immune Response Suppression and Protein Expression Inhibition

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Yuan ◽  
Shravani Balaji ◽  
Ivan B. Lomakin ◽  
Yong Xiong
Keyword(s):  
Immune Responses ◽  
Protein Expression ◽  
Vaccine Development ◽  
Nonstructural Protein ◽  
Global Gene Expression ◽  
Current Data ◽  
Host Protein ◽  
Host Cells ◽  
Live Attenuated Vaccine ◽  
Nonstructural Protein 1

Coronaviruses have brought severe challenges to public health all over the world in the past 20years. SARS-CoV-2, the causative agent of the COVID-19 pandemic that has led to millions of deaths, belongs to the genus beta-coronavirus. Alpha- and beta-coronaviruses encode a unique protein, nonstructural protein 1 (Nsp1) that both suppresses host immune responses and reduces global gene expression levels in the host cells. As a key pathogenicity factor of coronaviruses, Nsp1 redirects the host translation machinery to increase synthesis of viral proteins. Through multiple mechanisms, coronaviruses impede host protein expression through Nsp1, while escaping inhibition to allow the translation of viral RNA. In this review, we discuss current data about suppression of the immune responses and inhibition of protein synthesis induced by coronavirus Nsp1, as well as the prospect of live-attenuated vaccine development with virulence-attenuated viruses with mutations in Nsp1.

scholarly journals Zika NS1–induced ER remodeling is essential for viral replication

2019 ◽  
Vol 219 (2) ◽  
Author(s):  
Yali Ci ◽  
Zhong-Yu Liu ◽  
Na-Na Zhang ◽  
Yuqiang Niu ◽  
Yang Yang ◽  
...  
Keyword(s):  
Viral Replication ◽  
Zika Virus ◽  
Crucial Role ◽  
Nonstructural Protein ◽  
Membrane Binding ◽  
Membrane System ◽  
Model Membrane ◽  
Membrane Remodeling ◽  
Nonstructural Protein 1 ◽  
Replication Compartment

Zika virus (ZIKV), a recently emerged member of the flavivirus family, forms replication compartments at the ER during its lifecycle. The proteins that are responsible for the biogenesis of replication compartments are not well defined. Here, we show that Zika nonstructural protein 1 (NS1)–induced ER remodeling is essential for viral replication. NS1 expressed in the ER lumen induced ER perinuclear aggregation with an ultrastructure resembling that of the replication compartment. Data from model membrane system indicated that the membrane-binding and membrane-remodeling properties of NS1 depend on its hydrophobic insertion into the membrane. These findings demonstrate that NS1 plays a crucial role in flavivirus replication compartment formation by remodeling the ER structure.

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