scholarly journals Zika Virus Is Not Uniquely Stable at Physiological Temperatures Compared to Other Flaviviruses

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Leslie Goo ◽  
Kimberly A. Dowd ◽  
Alexander R. Y. Smith ◽  
Rebecca S. Pelc ◽  
Christina R. DeMaso ◽  
...  

ABSTRACT Zika virus (ZIKV) is a flavivirus that has emerged as a global health threat due in part to its association with congenital abnormalities. Other globally relevant flaviviruses include dengue virus (DENV) and West Nile virus (WNV). High-resolution structures of ZIKV reveal many similarities to DENV and suggest some differences, including an extended glycan loop (D. Sirohi, Z. Chen, L. Sun, T. Klose, T. C. Pierson, et al., 352:467–470, 2016, http://dx.doi.org/10.1126/science.aaf5316) and unique interactions among envelope (E) protein residues that were proposed to confer increased virion stability and contribute mechanistically to the distinctive pathobiology of ZIKV (V. A. Kostyuchenko, E. X. Lim, S. Zhang, G. Fibriansah, T. S. Ng, et al., Nature 533:425–428, 2016, http://dx.doi.org/10.1038/nature17994). However, in the latter study, virus stability was inferred by measuring the loss of infectivity following a short incubation period. Here, we rigorously assessed the relative stability of ZIKV, DENV, and WNV by measuring changes in infectivity following prolonged incubation at physiological temperatures. At 37°C, the half-life of ZIKV was approximately twice as long as the half-life of DENV (11.8 and 5.2 h, respectively) but shorter than that of WNV (17.7 h). Incubation at 40°C accelerated the loss of ZIKV infectivity. Increasing virion maturation efficiency modestly increased ZIKV stability, as observed previously with WNV and DENV. Finally, mutations at E residues predicted to confer increased stability to ZIKV did not affect virion half-life. Our results demonstrate that ZIKV is not uniquely stable relative to other flaviviruses, suggesting that its unique pathobiology is explained by an alternative mechanism. IMPORTANCE Zika virus (ZIKV) belongs to the Flavivirus genus, which includes other clinically relevant mosquito-borne pathogens such as dengue virus (DENV) and West Nile virus (WNV). Historically, ZIKV infection was characterized by a self-limiting, mild disease, but recent outbreaks have been associated with severe clinical complications, including Guillain-Barré syndrome and microcephaly, which are atypical of other flavivirus infections. Moreover, ZIKV has been detected in saliva, urine, and semen, and it may be sexually transmitted. Analysis of a high-resolution cryo-electron microscopic reconstruction of ZIKV hypothesized that the unusual stability of this virus contributes to its distinctive pathobiology. Here, we directly compared the stability of ZIKV to that of other flaviviruses following prolonged incubation in solution at physiological temperatures. We found that the stability of multiple ZIKV strains, including those from recent outbreaks, is intermediate between that of DENV and WNV, suggesting an alternative explanation for the unique clinical manifestations of ZIKV infection.

2019 ◽  
Vol 268 ◽  
pp. 53-55 ◽  
Author(s):  
José A. Boga ◽  
Marta E. Alvarez-Arguelles ◽  
Susana Rojo-Alba ◽  
Mercedes Rodríguez ◽  
María de Oña ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Himanshu Garg ◽  
Rose Yeh ◽  
Douglas M. Watts ◽  
Tugba Mehmetoglu-Gurbuz ◽  
Robert Resendes ◽  
...  

Abstract Background Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. Results Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. Conclusions Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.


2021 ◽  
Vol 12 ◽  
Author(s):  
Joshua A. Acklin ◽  
Javier D. Cattle ◽  
Arianna S. Moss ◽  
Julia A. Brown ◽  
Gregory A. Foster ◽  
...  

Antibody-dependent enhancement (ADE) is a phenomenon that occurs when cross-reactive antibodies generated from a previous flaviviral infection increase the pathogenesis of a related virus. Zika virus (ZIKV) is the most recent flavivirus introduced to the Western Hemisphere and has become a significant public health threat due to the unanticipated impact on the developing fetus. West Nile virus (WNV) is the primary flavivirus that circulates in North America, and we and others have shown that antibodies against WNV are cross-reactive to ZIKV. Thus, there is concern that WNV immunity could increase the risk of severe ZIKV infection, particularly during pregnancy. In this study, we examined the extent to which WNV antibodies could impact ZIKV pathogenesis in a murine pregnancy model. To test this, we passively transferred WNV antibodies into pregnant Stat2-/- mice on E6.5 prior to infection with ZIKV. Evaluation of pregnant dams showed weight loss following ZIKV infection; however, no differences in maternal weights or viral loads in the maternal brain, spleen, or spinal cord were observed in the presence of WNV antibodies. Resorption rates, and other fetal parameters, including fetal and placental size, were similarly unaffected. Further, the presence of WNV antibodies did not significantly alter the viral load or the inflammatory response in the placenta or the fetus in response to ZIKV. Our data suggest that pre-existing WNV immunity may not significantly impact the pathogenesis of ZIKV infection during pregnancy. Our findings are promising for the safety of implementing WNV vaccines in the continental US.


Author(s):  
Sisir Nandi ◽  
Aaliya Naaz ◽  
Mridula Saxena

Zika is an Aedes mosquito vector-borne pandemic viral disease. It is a goal for the scientists to destroy the virus completely by generating potent inhibitors. To explore the disease mechanism, various zika viral targets were explored. One of the major targets is Methyltransferase (Mtase), which is common with zika virus (ZIKV), dengue virus (DENV), and West Nile virus (WNV) belonging to the family of Flaviviridae. Therefore, an attempt has been made here to quest dengue virus and West Nile virus Mtase inhibitors, which could be repurposed on Zika virus inhibition by structure-based docking studies. The mode of interactions of 25 DENV and WNV inhibitors has been compared with natural reference drug sinefungin, which is a specific dengue virus and West Nile virus methyl transferase inhibitor. The docking results of compound numbers 4, 6, 10, 12, 13, 17, 18, and 20 exhibit the same mode of interaction with sinefungin. Therefore, these compounds could be proposed for a further experimental investigation to combat zika.


2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Federico Valdez ◽  
Julienne Salvador ◽  
Pedro M. Palermo ◽  
Jonathon E. Mohl ◽  
Kathryn A. Hanley ◽  
...  

ABSTRACTSchlafen 11 (Slfn11) is an interferon-stimulated gene that controls the synthesis of proteins by regulating tRNA abundance. Likely through this mechanism, Slfn11 has previously been shown to impair human immunodeficiency virus type 1 (HIV-1) infection and the expression of codon-biased open reading frames. Because replication of positive-sense single-stranded RNA [(+)ssRNA] viruses requires the immediate translation of the incoming viral genome, whereas negative-sense single-stranded RNA [(−)ssRNA] viruses carry at infection an RNA replicase that makes multiple translation-competent copies of the incoming viral genome, we reasoned that (+)ssRNA viruses will be more sensitive to the effect of Slfn11 on protein synthesis than (−)ssRNA viruses. To evaluate this hypothesis, we tested the effects of Slfn11 on the replication of a panel of ssRNA viruses in the human glioblastoma cell line A172, which naturally expresses Slfn11. Depletion of Slfn11 significantly increased the replication of (+)ssRNA viruses from theFlavivirusgenus, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV), but had no significant effect on the replication of the (−)ssRNA viruses vesicular stomatitis virus (VSV) (Rhabdoviridaefamily) and Rift Valley fever virus (RVFV) (Phenuiviridaefamily). Quantification of the ratio of genome-containing viral particles to PFU indicated that Slfn11 impairs WNV infectivity. Intriguingly, Slfn11 prevented WNV-induced downregulation of a subset of tRNAs implicated in the translation of 11.8% of the viral polyprotein. Low-abundance tRNAs might promote optimal protein folding and enhance viral infectivity, as previously reported. In summary, this study demonstrates that Slfn11 restricts flavivirus replication by impairing viral infectivity.IMPORTANCEWe provide evidence that the cellular protein Schlafen 11 (Slfn11) impairs replication of flaviviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV). However, replication of single-stranded negative RNA viruses was not affected. Specifically, Slfn11 decreases the infectivity of WNV potentially by preventing virus-induced modifications of the host tRNA repertoire that could lead to enhanced viral protein folding. Furthermore, we demonstrate that Slfn11 is not the limiting factor of this novel broad antiviral pathway.


2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Luh Ade Wilan Krisna

Virus Zika (ZIKV) adalah flavivirus yang berhubungan dengan dengue, virus demam kuning, virus Japanese encephalitis dan virus west nile. Virus tersebut menyebabkan infeksi melalui gigitan nyamuk yang dikenal sebagai demam zika atau penyakit zika. Virus zika baru-baru ini menarik perhatian dunia pada pertengahan tahun 2016 karena adanya explosive pandemic di berbagai negara, termasuk di Indonesia. Penelitian telah menemukan bukti bahwa Zika dapat berhubungan dengan cacat kelahiran dan kondisi syaraf seperti microcephaly dan sindrom Guillain-Barre pada orang dewasa. Kata kunci: Zika virus, flavivirus, microcephaly, Guillain-Barre Syndrome


2017 ◽  
Vol 8 ◽  
Author(s):  
Ángela Vázquez-Calvo ◽  
Nereida Jiménez de Oya ◽  
Miguel A. Martín-Acebes ◽  
Emilia Garcia-Moruno ◽  
Juan-Carlos Saiz

Cell ◽  
2009 ◽  
Vol 139 (7) ◽  
pp. 1243-1254 ◽  
Author(s):  
Abraham L. Brass ◽  
I-Chueh Huang ◽  
Yair Benita ◽  
Sinu P. John ◽  
Manoj N. Krishnan ◽  
...  

2016 ◽  
Vol 54 (4) ◽  
pp. 860-867 ◽  
Author(s):  
Jesse J. Waggoner ◽  
Benjamin A. Pinsky

Zika virus (ZIKV) is anAedesmosquito-borne flavivirus that emerged in Brazil in 2015 and then rapidly spread throughout the tropical and subtropical Americas. Based on clinical criteria alone, ZIKV cannot be reliably distinguished from infections with other pathogens that cause an undifferentiated systemic febrile illness, including infections with two common arboviruses, dengue virus and chikungunya virus. This minireview details the methods that are available to diagnose ZIKV infection.


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