scholarly journals A global map of the Zika virus phosphoproteome reveals host-driven regulation of viral budding

2021 ◽  
Author(s):  
Inessa Manuelyan ◽  
Anna M. Schmoker ◽  
Boyd L. Yount ◽  
Philip Eisenhauer ◽  
Judith I. Keller ◽  
...  

Flaviviruses are enveloped, positive-strand RNA viruses that cause millions of infections in the human population annually. Although Zika virus (ZIKV) had been detected in humans as early as the 1950s, its reemergence in South America in 2015 resulted in a global health crisis. While flaviviruses encode 10 proteins that can be post-translationally modified by host enzymes, little is known regarding post-translational modifications (PTMs) of the flavivirus proteome. We used mass spectrometry to comprehensively identify host-driven PTMs on the ZIKV proteome. This approach allowed us to identify 43 PTMs across 8 ZIKV proteins, including several that are highly conserved within the Flavivirus genus. Notably, we found two phosphosites on the ZIKV envelope protein that are functionally important for viral propagation and appear to regulate viral budding. Additionally, we discovered 115 host kinases that interacted with ZIKV proteins and determined that Bosutinib, an FDA-approved tyrosine kinase inhibitor that targets ZIKV interacting host kinases, impairs ZIKV growth. Thus, we have defined a high-resolution map of host-driven PTMs on ZIKV proteins as well as cellular interacting kinases, uncovered a novel mechanism of host driven-regulation of ZIKV budding, and identified an FDA-approved inhibitor of ZIKV growth.

Author(s):  
Sujit Pujhari ◽  
Jason L. Rasgon

Zika virus is a newly emergent mosquito-borne flavivirus. Once almost ignored epidemiologically, recent major outbreaks and links to neurological birth defects have focused attention on this neglected pathogen. We review the discovery, biology and symptomatology of Zika virus, what is known and not known about the mosquitoes that transmit the virus, conspiracy theories currently hampering control efforts, and potential avenues of Zika control. It is likely that Zika virus is here to stay in the Americas, so a thorough understanding of the complete epidemiological transmission cycle and potential effects on the human population will be critical for managing this new disease in the coming years.


2018 ◽  
Vol 33 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Hina Asad ◽  
David O. Carpenter

Abstract Zika is a vector-borne viral disease transmitted to humans primarily by Aedes aegypti mosquitoes. The increased climate instability has contributed to the emergence of infections carried by mosquitoes like dengue, chikungunya and zika. While infection with the zika virus is not new, the recent epidemic of microcephaly in Brazil and other countries in South America resulting from the infection of pregnant women with the zika virus raise a number of serious public health concerns. These include the question of how climate change affects the range of zika vectors, what can we do to shorten the length of mosquito season, how and why the symptoms of zika infection have changed and what can be done to reduce the burden of human disease from this infection? Another important question that needs to be answered is what are the factors that caused the zika virus to leave the non-human primates and/or other mammals and invade the human population?


2020 ◽  
Vol 21 (2) ◽  
pp. 492 ◽  
Author(s):  
Pharaoh Fellow Mwale ◽  
Chi-Hsin Lee ◽  
Liang-Tzung Lin ◽  
Sy-Jye Leu ◽  
Yun-Ju Huang ◽  
...  

Zika virus (ZIKV) is a new and emerging virus that has caused outbreaks worldwide. The virus has been linked to congenital neurological malformations in neonates and Guillain–Barré syndrome in adults. Currently there are no effective vaccines available. As a result, there is a great need for ZIKV treatment. In this study, we developed single chain variable fragment (scFv) antibodies that target the ZIKV envelope protein using phage display technology. We first induced an immune response in white leghorn laying hens against the ZIKV envelope (E) protein. Chickens were immunized and polyclonal immunoglobulin yolk (IgY) antibodies were extracted from egg yolks. A high-level titer of anti-ZIKV_E IgY antibodies was detected using enzyme-linked immunosorbent assay (ELISA) after the third immunization. The titer persisted for at least 9 weeks. We constructed two antibody libraries that contained 5.3 × 106 and 4.5 × 106 transformants. After biopanning, an ELISA phage assay confirmed the enrichment of specific clones. We randomly selected 26 clones that expressed ZIKV scFv antibodies and classified them into two groups, short-linker and long-linker. Of these, four showed specific binding activities toward ZIKV_E proteins. These data suggest that the polyclonal and monoclonal scFv antibodies have the diagnostic or therapeutic potential for ZIKV.


2020 ◽  
Vol 278 ◽  
pp. 197882
Author(s):  
Yongchao Zhou ◽  
Dong Chen ◽  
Lan Yang ◽  
Weiwei Zou ◽  
Zhiliang Duan ◽  
...  

2002 ◽  
Vol 76 (11) ◽  
pp. 5729-5736 ◽  
Author(s):  
Oliver Lung ◽  
Marcel Westenberg ◽  
Just M. Vlak ◽  
Douwe Zuidema ◽  
Gary W. Blissard

ABSTRACT GP64, the major envelope glycoprotein of budded virions of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), is involved in viral attachment, mediates membrane fusion during virus entry, and is required for efficient virion budding. Thus, GP64 is essential for viral propagation in cell culture and in animals. Recent genome sequences from a number of baculoviruses show that only a subset of closely related baculoviruses have gp64 genes, while other baculoviruses have a recently discovered unrelated envelope protein named F. F proteins from Lymantria dispar MNPV (LdMNPV) and Spodoptera exigua MNPV (SeMNPV) mediate membrane fusion and are therefore thought to serve roles similar to that of GP64. To determine whether F proteins are functionally analogous to GP64 proteins, we deleted the gp64 gene from an AcMNPV bacmid and inserted F protein genes from three different baculoviruses. In addition, we also inserted envelope protein genes from vesicular stomatitis virus (VSV) and Thogoto virus. Transfection of the gp64-null bacmid DNA into Sf9 cells does not generate infectious particles, but this defect was rescued by introducing either the F protein gene from LdMNPV or SeMNPV or the G protein gene from VSV. These results demonstrate that baculovirus F proteins are functionally analogous to GP64. Because baculovirus F proteins appear to be more widespread within the family and are much more divergent than GP64 proteins, gp64 may represent the acquisition of an envelope protein gene by an ancestral baculovirus. The AcMNPV pseudotyping system provides an efficient and powerful method for examining the functions and compatibilities of analogous or orthologous viral envelope proteins, and it could have important biotechnological applications.


2016 ◽  
Vol 19 (5) ◽  
pp. 696-704 ◽  
Author(s):  
Lianpan Dai ◽  
Jian Song ◽  
Xishan Lu ◽  
Yong-Qiang Deng ◽  
Abednego Moki Musyoki ◽  
...  

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