Envelope protein ubiquitination drives entry and pathogenesis of Zika virus

Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South American has caused severe human congenital and neurologic disorders. Thus, it is vitally important to figure out inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost ability to inhibit the infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.

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USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination

Viruses ◽

10.3390/v13102029 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2029

Author(s):

Yingchong Wang ◽

Qin Li ◽

Dingwen Hu ◽

Daolong Gao ◽

Wenbiao Wang ◽

...

Keyword(s):

Host Resistance ◽

Zika Virus ◽

Envelope Protein ◽

Host Protein ◽

Zikv Infection ◽

Potential Therapeutic Target ◽

Treatment And Prevention ◽

Protein Ubiquitination ◽

Neurologic Disorders ◽

Novel Host

Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South America has caused severe human congenital and neurologic disorders. Thus, it is vitally important to determine the inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to the ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost the ability to inhibit infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.

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Cross-reactive dengue virus-derived monoclonal antibodies to Zika virus envelope protein: Panacea or Pandora’s box?

BMC Infectious Diseases ◽

10.1186/s12879-018-3572-0 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 3

Author(s):

Shannon A. Gunawardana ◽

Robert H. Shaw

Keyword(s):

Monoclonal Antibodies ◽

Dengue Virus ◽

Zika Virus ◽

Envelope Protein ◽

Virus Envelope ◽

Virus Envelope Protein

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Zika Virus Envelope Protein and Antibody Complexes

Subcellular Biochemistry - Virus Protein and Nucleoprotein Complexes ◽

10.1007/978-981-10-8456-0_7 ◽

2018 ◽

pp. 147-168 ◽

Cited By ~ 3

Author(s):

Lianpan Dai ◽

Qihui Wang ◽

Hao Song ◽

George Fu Gao

Keyword(s):

Zika Virus ◽

Envelope Protein ◽

Virus Envelope ◽

Virus Envelope Protein

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Polysaccharides like pentagalloylglucose, parishin a and stevioside inhibits the viral entry by binding the Zika virus envelope protein

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2020.1797538 ◽

2020 ◽

pp. 1-13

Author(s):

Nitin Sharma ◽

Prateek Kumar ◽

Rajanish Giri

Keyword(s):

Viral Entry ◽

Zika Virus ◽

Envelope Protein ◽

Virus Envelope ◽

Virus Envelope Protein

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Expression, Purification, and Characterization of Anti-Zika virus Envelope Protein: Polyclonal and Chicken-Derived Single Chain Variable Fragment Antibodies

International Journal of Molecular Sciences ◽

10.3390/ijms21020492 ◽

2020 ◽

Vol 21 (2) ◽

pp. 492 ◽

Cited By ~ 1

Author(s):

Pharaoh Fellow Mwale ◽

Chi-Hsin Lee ◽

Liang-Tzung Lin ◽

Sy-Jye Leu ◽

Yun-Ju Huang ◽

...

Keyword(s):

Zika Virus ◽

Envelope Protein ◽

Therapeutic Potential ◽

Specific Binding ◽

Enzyme Linked Immunosorbent Assay ◽

Single Chain Variable Fragment ◽

Single Chain ◽

Virus Envelope ◽

Phage Display Technology ◽

High Level

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.

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