2. Academic Validation
  3. KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry

KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry

  • Virol J. 2024 Aug 8;21(1):181. doi: 10.1186/s12985-024-02454-3.
Jiayuan Sun # 1,  Yige Ding # 1,  Qian Zhou 1,  Peter Kalds 2,  Jianlin Han 2,  Keshan Zhang 3,  Yinghui Wei 1 4 5,  Weiwei Wu 6,  Xiaolong Wang 7 8 9,  Wenxin Zheng 10
Affiliations

Affiliations

  • 1 International Joint Agriculture Research Center for Animal Bio-breeding, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
  • 2 Yazhouwan National Laboratory, Sanya, 572024, China.
  • 3 Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan, 528225, China.
  • 4 Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, 712100, China.
  • 5 School of Future Technology on Bio-breeding, Northwest A&F University, Yangling, 712100, China.
  • 6 Xinjiang Academy of Animal Sciences, Urumqi, Xinjiang, 830011, China.
  • 7 International Joint Agriculture Research Center for Animal Bio-breeding, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China. xiaolongwang@nwafu.edu.cn.
  • 8 Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, 712100, China. xiaolongwang@nwafu.edu.cn.
  • 9 School of Future Technology on Bio-breeding, Northwest A&F University, Yangling, 712100, China. xiaolongwang@nwafu.edu.cn.
  • 10 Xinjiang Academy of Animal Sciences, Urumqi, Xinjiang, 830011, China. zwx2020@126.com.
  • # Contributed equally.
PMID: 39118175 DOI: 10.1186/s12985-024-02454-3
Abstract

The orf virus (ORFV) poses a serious threat to the health of domestic small ruminants (i.e., sheep and goats) and humans on a global scale, causing around $150 million in annual losses to livestock industry. However, the host factors involved in ORFV Infection and replication are still elusive. In this study, we compared the RNA-seq profiles of ORFV-infected or non-infected sheep testicular interstitial cells (STICs) and identified a novel host gene, potassium voltage-gated channel subfamily E member 4 (KCNE4), as a key host factor involved in the ORFV Infection. Both RNA-seq data and RT-qPCR assay revealed a significant increase in the expression of KCNE4 in the infected STICs from 9 to 48 h post Infection (hpi). On the Other hand, the RT-qPCR assay detected a decrease in ORFV copy number in both the STICs transfected by KCNE4 siRNA and the KCNE4 knockout (KO) HeLa cells after the ORFV Infection, together with a reduced fluorescence ratio of ORFV-GFP in the KO HeLa cells at 24 hpi, indicating KCNE4 to be critical for the ORFV Infection. Furthermore, the attachment and internalization assays showed decreased ORFV attachment, internalization, replication, and release by the KO HeLa cells, demonstrating a potential inhibition of ORFV entry into the cells by KCNE4. Pretreatment with the KCNE4 inhibitors such as quinidine and fluoxetine significantly repressed the ORFV Infection. All our findings reveal KCNE4 as a novel host regulator of the ORFV entry and replication, shedding new insight into the interactive mechanism of ORFV Infection. The study also highlights the K+ channels as possible druggable targets to impede viral Infection and disease.

Keywords

KCNE4; Inhibitor; Orf virus; RNA-seq; Viral entry.

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