Japanese Encephalitis Virus infection induces inflammation of swine testis through RIG-I—NF-ĸB signaling pathway

Zheng, Bohan; Wang, Xugang; Liu, Yixin; Li, Yunchuan; Long, Siwen; Gu, Changqin; Ye, Jing; Xie, Shengsong; Cao, Shengbo

doi:10.1016/j.vetmic.2019.108430

Cited by 25 publications

(23 citation statements)

References 23 publications

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“…Zheng and colleagues showed that the JEV infection induces inflammation of pig testicles by activating RIG-I/NF-kB pathway signaling [98]. This also leads to orchitis, which is a type of chronic inflammation in the testes caused by viral or bacterial infections, associated with pain, swelling, along with blood and swelling in prostate ejaculate [81,99].…”

Section: The Immune System Of Testis During Viral Infectionmentioning

confidence: 99%

“…This also leads to orchitis, which is a type of chronic inflammation in the testes caused by viral or bacterial infections, associated with pain, swelling, along with blood and swelling in prostate ejaculate [81,99]. Testes infection with JEV showed a differential production of pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8, chemokine RANTES, and TNF-α, as well as an increased presence of NS5 (non-structural protein of the virus), RIG-I, TLR3 and -7 [98]. Smith and colleagues showed that a 43-year-old patient presented signs of encephalitis and orchitis caused by WNV [100].…”

Section: The Immune System Of Testis During Viral Infectionmentioning

confidence: 99%

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The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

Almeida

Braz-de-Melo

Santos

et al. 2020

Cells

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Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.

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Section: The Immune System Of Testis During Viral Infectionmentioning

confidence: 99%

Section: The Immune System Of Testis During Viral Infectionmentioning

confidence: 99%

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

Almeida

Braz-de-Melo

Santos

et al. 2020

Cells

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show abstract

“…Our results highlight the power of CRISPR/Cas9-based screening for functional analyses in pigs, and we present in Figure 7 While genome-scale CRISPR/Cas9 mutagenesis methods obviously facilitate gene functional studies in both cellular and animal models [19][20][21][22][23][24] , and the ability to programmably target the entire coding or regulatory genome represents a significant advance over spontaneous or random mutagenesis, genome-scale CRISPR/Cas9 approaches share with classical forward genetic screens the requirement for an assay to enrich for cells exhibiting the phenotype of interest [37][38][39] . JEV causes encephalitis in humans and reproductive disorders in pigs, the latter leading to substantial economic losses 10 . In the present study, we developed a series of genome-scale pig CRISPR/Cas9 knockout library (PigGeCKO) resources that facilitate the pooled screening of genes that prevent JEV invasion or replication, thereby inhibiting JEV-induced cell death in porcine cells.…”

Section: Discussionmentioning

confidence: 99%

“…One limitation of this study is that it did not specifically address issues of potential cell specificity of JEV infection. Although PK-15 cells are susceptible to JEV, this virus primarily infects nerve cells and germ cells 10,25 . It is also important to note that JEV can infect many different types of cells from highly divergent species, including but not limited to Vero cells, BHK-21 cells, and mouse neuro 2a cells 14 .…”

Section: Discussionmentioning

confidence: 99%

CRISPR screening of porcine sgRNA library identified host factors essential for Japanese encephalitis virus replication

Zhao

Liu

Xiao

et al. 2019

Preprint

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Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, key host genes involved in the JEV life cycle and cell death are poorly understood. Here, we designed 85,674 single guide RNAs (sgRNAs) targeting 17,743 protein-coding genes, 11,053 long ncRNAs (lncRNAs), and 551 microRNAs (miRNAs) in the porcine genome, and subsequently developed a porcine sgRNA library and genome-scale CRISPR/Cas9 knockout (PigGeCKO) system. These sgRNAs were delivered into porcine kidney-15 (PK-15) cells that constitutively express Cas9, positive selection screening of the resulting PigGeCKO cell collection for resistance to JEV-induced cell death led to the identification of several previously unreported genes required for JEV infection. We conducted follow-up studies to verify the dependency of JEV on these genes, and identified functional contributions for six of the many candidate JEV-related host genes, including an endoplasmic reticulum membrane protein complex subunit 3 (EMC3) and calreticulin (CALR). Additionally, we identified that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPG sulfurylation, facilitated JEV entry into PK-15 cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this work deepens our basic understanding of flavivirus infection and identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to prevent and treat diseases caused by Japanese encephalitis virus.

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“…Pigs are readily infected with JEV and can develop high levels of viremia 7,8 . JEV infection is usually asymptomatic in adult pigs, but manifestations of abortion, still-birth, and birth defects, including central nervous system defects, are not unusual following infection in pregnant swine, which can result in substantial economic losses to pork producers 9,10 . Accordingly, JEV outbreaks represent a major threat to both public health and the agricultural economy, especially in areas with low vaccine coverage and/or limited diagnostic capacity 11 .…”

mentioning

confidence: 99%

CRISPR screening of porcine sgRNA library identifies host factors associated with Japanese encephalitis virus replication

et al. 2020

Self Cite

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Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, the host factors critical for its entry, replication, and assembly are poorly understood. Here, we design a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library containing 85,674 single guide RNAs targeting 17,743 protein-coding genes, 11,053 long ncRNAs, and 551 microRNAs. Subsequently, we use the PigGeCKO library to identify key host factors facilitating JEV infection in porcine cells. Several previously unreported genes required for JEV infection are highly enriched post-JEV selection. We conduct follow-up studies to verify the dependency of JEV on these genes, and identify functional contributions for six of the many candidate JEV-related host genes, including EMC3 and CALR. Additionally, we identify that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPGs sulfurylation, facilitate JEV entry into porcine cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this study identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to treat and prevent diseases caused by JEV.

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Japanese Encephalitis Virus infection induces inflammation of swine testis through RIG-I—NF-ĸB signaling pathway

Cited by 25 publications

References 23 publications

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

CRISPR screening of porcine sgRNA library identified host factors essential for Japanese encephalitis virus replication

CRISPR screening of porcine sgRNA library identifies host factors associated with Japanese encephalitis virus replication

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