scholarly journals Asian lineage of Zika virus RNA pseudoknot may induce ribosomal frameshift and produce a new neuroinvasive protein ZIKV-NS1’

2017 ◽  
Author(s):  
Tiago Tambonis ◽  
Vinícius G. Contessoto ◽  
Cíntia Bittar ◽  
Marília F. Calmon ◽  
Maurício L. Nogueira ◽  
...  
Keyword(s):  
Zika Virus ◽  
Ns1 Protein ◽  
Ribosomal Frameshift ◽  
Zikv Infection ◽  
Potential Target ◽  
Virus Rna ◽  
Alternative Protein ◽  
Asian Lineage ◽  
Rna Pseudoknot

Zika virus (ZIKV) is a threat to humanity, and understanding its neuroinvasiveness is a major challenge. Microcephaly observed in neonates in Brazil is associated with ZIKV that belongs to the Asian lineage. What distinguishes the neuroinvasiveness between the RNA lineages from Asia and Africa is still unknown. Here we identify an aspect that may explain the different behavior between the two lineages. The distinction between the two groups is the occurrence of an alternative protein NS1’ (ZIKV-NS1’), which happens through a pseudoknot in the virus RNA that induces a ribosomal frameshift. Presence of NS1’ protein is also observed in other Flavivirus that are neuroinvasive, and when NS1’ production issuppressed, neuroinvasiveness is reduced.1 This evidence gives grounds to suggest that the ZIKV-NS1’ occurring in the Asian lineage is responsible for neuro-tropism, which causes the neuro-pathologies associated with ZIKV infection, of which microcephaly is the most dev astating. The existence of ZIKV-NS1’, which only exists in the Asian lineage, was inferred through bioinformatic methods, and it has yet to be experimentally observed. If its occurrence is confirmed, it will be a potential target in fighting the neuro-diseases associated with ZIKV.

scholarly journals TRiC/CCT Complex, a Binding Partner of NS1 Protein, Supports the Replication of Zika Virus in Both Mammalians and Mosquitoes

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 519
Author(s):  
Yuchen Wang ◽  
Ryuta Uraki ◽  
Jesse Hwang ◽  
Erol Fikrig
Keyword(s):  
Mass Spectrometry ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Host Factors ◽  
Ns1 Protein ◽  
Zikv Infection ◽  
Binding Partner ◽  
Promising Therapeutic Target ◽  
Critical Components ◽  
Congenital Microcephaly

Mosquito-borne Zika virus (ZIKV) can cause congenital microcephaly and Guillain–Barré syndrome, among other symptoms. Specific treatments and vaccines for ZIKV are not currently available. To further understand the host factors that support ZIKV replication, we used mass spectrometry to characterize mammalian proteins that associate with the ZIKV NS1 protein and identified the TRiC/CCT complex as an interacting partner. Furthermore, the suppression of CCT2, one of the critical components of the TRiC/CCT complex, inhibited ZIKV replication in both mammalian cells and mosquitoes. These results highlight an important role for the TRiC/CCT complex in ZIKV infection, suggesting that the TRiC/CCT complex may be a promising therapeutic target.

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.

scholarly journals Transcriptional signatures of Zika virus infection in astrocytes

2021 ◽  
Author(s):  
Blake Schouest ◽  
Tiffany A. Peterson ◽  
Dawn M. Szeltner ◽  
Elizabeth A. Scheef ◽  
Melody Baddoo ◽  
...  
Keyword(s):  
Zika Virus ◽  
Rhesus Macaques ◽  
Response Patterns ◽  
Zikv Infection ◽  
African Lineage ◽  
Important Target ◽  
Asian Lineage ◽  
Human Infections ◽  
The Brain ◽  
Infant Rhesus

AbstractAstrocytes are an early and important target of Zika virus (ZIKV) infection in the developing brain, but the impacts of infection on astrocyte function remain controversial. Given that nonhuman primate (NHP) models of ZIKV infection replicate aspects of neurologic disease seen in human infections, we cultured primary astrocytes from the brain tissue of infant rhesus macaques and then infected the cells with Asian or African lineage ZIKV to identify transcriptional patterns associated with infection in these cells. The African lineage virus appeared to have greater infectivity and promote stronger antiviral signaling, but infection by either strain ultimately produced typical virus response patterns. Both viruses induced hypoxic stress, but the Asian lineage strain additionally had an effect on metabolic and lipid biosynthesis pathways. Together, these findings describe an NHP astrocyte model that may be used to assess transcriptional signatures following ZIKV infection.

scholarly journals Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016

2016 ◽  
Vol 21 (32) ◽  
Author(s):  
Luisa Barzon ◽  
Monia Pacenti ◽  
Elisa Franchin ◽  
Enrico Lavezzo ◽  
Marta Trevisan ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Zika Virus ◽  
Laboratory Testing ◽  
Zikv Infection ◽  
Infection Dynamics ◽  
Virus Rna

We describe the dynamics of Zika virus (ZIKV) infection in a man in his early 40s who developed fever and rash after returning from Haiti to Italy, in January 2016. Follow-up laboratory testing demonstrated detectable ZIKV RNA in plasma up to day 9 after symptom onset and in urine and saliva up to days 15 and 47, respectively. Notably, persistent shedding of ZIKV RNA was demonstrated in semen, still detectable at 181 days after onset.

scholarly journals The Extrinsic Incubation Period of Zika Virus in Florida Mosquitoes Aedes aegypti and Ae. albopictus

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1252
Author(s):  
Rebecca A. Zimler ◽  
Barry W. Alto
Keyword(s):  
Aedes Aegypti ◽  
Incubation Period ◽  
Health Risks ◽  
Zika Virus ◽  
Mosquito Vectors ◽  
Zikv Infection ◽  
Infected Blood ◽  
Extrinsic Incubation Period ◽  
Asian Lineage ◽  
Blood Meals

The Asian genotype of Zika virus (ZIKV) emerged in Brazil in 2015 and subsequently spread throughout the Americas. In July 2016, Florida experienced its first locally acquired ZIKV infection in the continental U.S. Concerns about health risks from ZIKV infection have increased the need to investigate the interactions between potential mosquito vectors and ZIKV. The time it takes for an arbovirus to propagate within a mosquito, and become transmissible, is the extrinsic incubation period (EIP). The EIP for potential mosquito vectors in Florida is unknown. To address this gap in the understanding of ZIKV epidemiology, Florida Aedes aegypti (L.) and Ae. albopictus (Skuse) were orally exposed to ZIKV infected blood meals and fully engorged mosquitoes were held at a constant temperature of 28 °C through the duration of the experiment. Saliva expectorates were collected from cohorts of mosquitoes and tested for the presence of ZIKV at three-day intervals over a period of 24 days to allow for an evaluation of the EIP of the emergent Asian lineage of ZIKV. High rates of infected bodies in Ae. albopictus (75–94%) and Ae. aegypti (68–86%) were observed throughout the incubation period, which did not differ by species. Higher rates of disseminated infection were observed later during the incubation period but did not differ between species. We calculated the 50% EIP to be shorter in Ae. albopictus than Ae. aegypti (16.2 and 18.2 days post infection, respectively). The competence for ZIKV observed in both species may contribute to high rates of ZIKV transmission in Florida populations.

scholarly journals High correlation between Zika virus NS1 antibodies and neutralizing antibodies in selected serum samples from normal healthy Thais

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wannapa Sornjai ◽  
Suwipa Ramphan ◽  
Nitwara Wikan ◽  
Prasert Auewarakul ◽  
Duncan R. Smith
Keyword(s):  
Southeast Asia ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Ns1 Protein ◽  
Serum Samples ◽  
Zikv Infection ◽  
Ns1 Antigen ◽  
Cross Neutralization ◽  
Immunological Protection

Abstract Despite the widespread presence of the mosquito transmitted Zika virus (ZIKV) over much of Southeast Asia, the number of reported cases remains low. One possibility is that residents in Southeast Asia are immunologically protected, although the nature of any such protection remains unclear. This study sought to investigate the presence of antibodies directed to ZIKV NS1 protein in a selected sub-set of samples from a well characterized cohort of serum samples from normal, healthy Thais that had been previously characterized for the presence of neutralizing antibodies to ZIKV, DENV 1-4, and JEV. Because of similarities in molecular weight between the flavivirus E and NS1 proteins, an immunoblot system was established in which the NS1 antigen was not denatured, allowing detection of the dimer form of NS1, distinctly clear from the migration position of the E and NS1 monomer proteins. The results showed that antibodies to ZIKV NS1 protein were only detected in samples with ZIKV neutralizing antibodies (27/30 samples), and no sample (0/30) with a ZIKV plaque reduction neutralization test (PRNT)90 < 20 showed evidence of anti-ZIKV NS1 antibodies. The high correlation between the presence of ZIKV NS1 antibodies and ZIKV PRNT suggests that immunological protection against ZIKV infection in Thailand arises from prior exposure to ZIKV, and not through cross neutralization.

scholarly journals Monoclonal Antibodies against Zika Virus NS1 Protein Confer Protection via Fcγ Receptor-Dependent and -Independent Pathways

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Yu ◽  
Xinglong Liu ◽  
Xianmiao Ye ◽  
Wan Su ◽  
Xiaoyan Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Zika Virus ◽  
Nonstructural Protein ◽  
Effector Function ◽  
Protective Effects ◽  
Ns1 Protein ◽  
Fcγ Receptor ◽  
Zikv Infection ◽  
Effector Cells ◽  
Nonstructural Protein 1

ABSTRACT Zika virus (ZIKV) infection during pregnancy causes congenital defects such as fetal microcephaly. Monoclonal antibodies (MAbs) against the nonstructural protein 1 (NS1) have the potential to suppress ZIKV pathogenicity without enhancement of disease, but the pathways through which they confer protection remain obscure. Here, we report two types of NS1-targeted human MAbs that inhibit ZIKV infection through distinct mechanisms. MAbs 3G2 and 4B8 show a better efficacy than MAb 4F10 in suppressing ZIKV infection in C57BL/6 neonatal mice. Unlike MAb 4F10 that mainly triggers antibody-dependent cell-mediated cytotoxicity (ADCC), MAbs 3G2 and 4B8 not only trigger ADCC but inhibit ZIKV infection without Fcγ receptor-bearing effector cells, possibly at postentry stages. Destroying the Fc-mediated effector function of MAbs 3G2 and 4B8 reduces but does not abolish their protective effects, whereas destroying the effector function of MAb 4F10 eliminates the protective effects, suggesting that MAbs 3G2 and 4B8 engage both Fcγ receptor-dependent and -independent pathways. Further analysis reveals that MAbs 3G2 and 4B8 target the N-terminal region of NS1 protein, whereas MAb 4F10 targets the C-terminal region, implying that the protective efficacy of an NS1-targeted MAb may be associated with its epitope recognition. Our results illustrate that NS1-targeted MAbs have multifaceted protective effects and provide insights for the development of NS1-based vaccines and therapeutics. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne flavivirus that has been linked to congenital microcephaly during recent epidemics. No licensed antiviral drug or vaccine is available. Monoclonal antibodies (MAbs) against the nonstructural protein 1 (NS1) inhibit ZIKV pathogenicity but do not enhance the disease as envelope protein-targeted MAbs do. However, the protection mechanisms are not fully understood. Here, we show that in the presence or absence of Fcγ receptor-bearing effector cells, NS1-targeted human MAbs 3G2 and 4B8 inhibit ZIKV infection. Compared to MAb 4F10 that has no inhibitory effects without effector cells, 3G2 and 4B8 confer better protection in ZIKV-infected neonatal mice. Destroying the Fc-mediated effector function reduces but does not abolish the protection of 3G2 and 4B8, suggesting that they engage both Fcγ receptor-dependent and -independent pathways. The protective efficacy of NS1-targeted MAbs may be associated with their epitope recognition. Our findings will help to develop NS1-based vaccines and therapeutics.

Pregnancy, the placenta and Zika virus (ZIKV) infection

2016 ◽  
Vol 37 (4) ◽  
pp. 170 ◽  
Author(s):  
William Rawlinson
Keyword(s):  
Zika Virus ◽  
Yellow Fever Virus ◽  
West African ◽  
Structural Proteins ◽  
South American ◽  
East African ◽  
Zikv Infection ◽  
Tick Borne Encephalitis ◽  
The Family ◽  
Asian Lineage

Zika virus (ZIKV) infections have been recognised in Africa and Asia since 1940. The virus is in the family Flaviviridae and genus Flavivirus, along with Dengue, Japanese encephalitis virus, Tick borne encephalitis, West Nile virus, and Yellow fever virus. These viruses share biological characteristics of an envelope, icosahedral nucleocapsid, and a non-segmented, positive sense, single-strand RNA genome of ~10kb encoding three structural proteins (capsid C pre-membrane/membrane PrM/M, envelope E), and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). ZIKV has three known genotypes; the West African (Nigerian cluster), East African (MR766 prototype cluster), and Asian strains. Virus sequencing from the most recent South American outbreak suggests this virus is related to the 2013 French Polynesian isolates of Asian lineage.

scholarly journals Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016

2016 ◽  
Vol 21 (32) ◽  
Author(s):  
Emanuele Nicastri ◽  
Concetta Castilletti ◽  
Giuseppina Liuzzi ◽  
Marco Iannetta ◽  
Maria R Capobianchi ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Zika Virus ◽  
Sexual Transmission ◽  
Erythematous Rash ◽  
Zikv Infection ◽  
Virus Rna ◽  
History Of ◽  
Vector Borne

A man in his early 30s reported in January 2016 a history of fever, asthenia and erythematous rash during a stay in Haiti. On his return to Italy, ZIKV RNA was detected in his urine and saliva 91 days after symptom onset, and in his semen on day 188, six months after symptom onset. Our findings support the possibility of sexual transmission of ZIKV and highlight the importance of continuing to investigate non-vector-borne ZIKV infection.

scholarly journals Spread of the pandemic Zika virus lineage is associated with NS1 codon usage adaptation in humans

2015 ◽  
Author(s):  
Caio Cesar de Melo Freire ◽  
Atila Iamarino ◽  
Daniel Ferreira de Lima Neto ◽  
Amadou Alpha Sall ◽  
Paolo Marinho de Andrade Zanotto
Keyword(s):  
South America ◽  
Codon Usage ◽  
20Th Century ◽  
Zika Virus ◽  
Pacific Islands ◽  
Urban Expansion ◽  
Housekeeping Genes ◽  
Ns1 Protein ◽  
The Pacific ◽  
Asian Lineage

Zika virus (ZIKV) infections were more common in the zoonotic cycle until the end of the 20th century with few human cases in Africa and Southeastern Asia. Recently, the Asian lineage of ZIKV is spreading along human-to-human chains of transmission in the Pacific Islands and in South America. To better understand its recent urban expansion, we compared genetic differences among the lineages. Herein we show that the recent Asian lineage spread is associated with significant NS1 codon usage adaptation to human housekeeping genes, which could facilitate viral replication and increase viral titers. These findings were supported by a significant correlation with growth in Malthusian fitness. Furthermore, we predicted several epitopes in the NS1 protein that are shared between ZIKV and Dengue. Our results imply in a significant dependence of the recent human ZIKV spread on NS1 translational selection.

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