Mosquito defensins enhance Japanese encephalitis virus infection by facilitating virus adsorption and entry within mosquito

AbstractJapanese encephalitis virus (JEV) is a viral zoonosis which can cause viral encephalitis, death and disability. Culex is the main vector of JEV, but little is known about JEV transmission by this kind of mosquito. Here, we found that mosquito defensin facilitated the adsorption of JEV on target cells via both direct and indirect pathways. Mosquito defensin bound the ED III domain of viral E protein and directly mediated efficient virus adsorption on the target cell surface, Lipoprotein receptor-related protein 2 expressed on the cell surface is the receptor affecting defensin dependent adsorption. Mosquito defensin also indirectly down-regulated the expression of an antiviral protein, HSC70B. As a result, mosquitos defensin enhances JEV infection in salivary gland while increasing the possibility of viral transmission by mosquito. These findings demonstrate that the novel effects of mosquito defensin in JEV infection and the mechanisms through which the virus exploits mosquito defensin for infection and transmission.

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Mosquito Defensins Enhance Japanese Encephalitis Virus Infection by Facilitating Virus Adsorption and Entry within the Mosquito

Journal of Virology ◽

10.1128/jvi.01164-20 ◽

2020 ◽

Vol 94 (21) ◽

Author(s):

Ke Liu ◽

Changguang Xiao ◽

Shumin Xi ◽

Muddassar Hameed ◽

Abdul Wahaab ◽

...

Keyword(s):

Cell Surface ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Encephalitis Virus ◽

Target Cells ◽

Lipoprotein Receptor ◽

Related Protein ◽

E Protein ◽

Virus Adsorption ◽

Lipoprotein Receptor Related Protein

ABSTRACT Japanese encephalitis virus (JEV) is a viral zoonosis that can cause viral encephalitis, death, and disability. Although the Culex mosquito is the primary vector of JEV, little is known about JEV transmission by this kind of mosquito. Here, we found that mosquito defensin facilitated the adsorption of JEV on target cells via the defensin/lipoprotein receptor-related protein 2 (LRP2) axis. Mosquito defensin bound the ED III domain of the viral envelope (E) protein and directly mediated efficient virus adsorption on the target cell surface; the receptor LRP2, which is expressed on the cell surface, affected defensin-dependent adsorption. As a result, mosquito defensin enhanced JEV infection in the salivary gland, increasing the possibility of viral transmission by mosquitoes. These findings demonstrate the novel role of mosquito defensin in JEV infection and the mechanisms through which the virus exploits mosquito defensin for infection and transmission. IMPORTANCE In this study, we observed the complex roles of mosquito defensin in JEV infection; mosquito defensin exhibited a weak antiviral effect but strongly enhanced binding. In the latter, defensin directly binds the ED III domain of the viral E protein and promotes the adsorption of JEV to target cells by interacting with lipoprotein receptor-related protein 2 (LRP2), thus accelerating virus entry. Together, our results indicate that mosquito defensin plays an important role in facilitating JEV infection and potential transmission.

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Mosquito defensin facilitates Japanese encephalitis virus infection by downregulating the C6/36 cell-surface antiviral protein HSC70B

Veterinary Microbiology ◽

10.1016/j.vetmic.2020.108971 ◽

2021 ◽

Vol 253 ◽

pp. 108971

Author(s):

Ke Liu ◽

Fengxiang Hou ◽

Abdul Wahaab ◽

Lei Kang ◽

Fengyu Xie ◽

...

Keyword(s):

Virus Infection ◽

Cell Surface ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Encephalitis Virus ◽

Antiviral Protein ◽

Japanese Encephalitis Virus Infection

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Inhibition of Japanese encephalitis virus infection by the host zinc-finger antiviral protein

PLoS Pathogens ◽

10.1371/journal.ppat.1007166 ◽

2018 ◽

Vol 14 (7) ◽

pp. e1007166 ◽

Cited By ~ 35

Author(s):

Hsin-Ping Chiu ◽

Han Chiu ◽

Chao-Fu Yang ◽

Yi-Ling Lee ◽

Feng-Lan Chiu ◽

...

Keyword(s):

Virus Infection ◽

Japanese Encephalitis Virus ◽

Zinc Finger ◽

Japanese Encephalitis ◽

Encephalitis Virus ◽

Antiviral Protein ◽

Japanese Encephalitis Virus Infection

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Early Events in Japanese Encephalitis Virus Infection: Viral Entry

Pathogens ◽

10.3390/pathogens7030068 ◽

2018 ◽

Vol 7 (3) ◽

pp. 68 ◽

Cited By ~ 10

Author(s):

Sang-Im Yun ◽

Young-Min Lee

Keyword(s):

Cell Surface ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Clinical Manifestations ◽

Encephalitis Virus ◽

Host Cells ◽

Target Cells ◽

Major Public Health Problem ◽

Viral Glycoprotein ◽

Positive Strand Rna

Japanese encephalitis virus (JEV), a mosquito-borne zoonotic flavivirus, is an enveloped positive-strand RNA virus that can cause a spectrum of clinical manifestations, ranging from mild febrile illness to severe neuroinvasive disease. Today, several killed and live vaccines are available in different parts of the globe for use in humans to prevent JEV-induced diseases, yet no antivirals are available to treat JEV-associated diseases. Despite the progress made in vaccine research and development, JEV is still a major public health problem in southern, eastern, and southeastern Asia, as well as northern Oceania, with the potential to become an emerging global pathogen. In viral replication, the entry of JEV into the cell is the first step in a cascade of complex interactions between the virus and target cells that is required for the initiation, dissemination, and maintenance of infection. Because this step determines cell/tissue tropism and pathogenesis, it is a promising target for antiviral therapy. JEV entry is mediated by the viral glycoprotein E, which binds virions to the cell surface (attachment), delivers them to endosomes (endocytosis), and catalyzes the fusion between the viral and endosomal membranes (membrane fusion), followed by the release of the viral genome into the cytoplasm (uncoating). In this multistep process, a collection of host factors are involved. In this review, we summarize the current knowledge on the viral and cellular components involved in JEV entry into host cells, with an emphasis on the initial virus-host cell interactions on the cell surface.

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