Dual-barrier mechanism of superinfection exclusion in Newcastle disease virus: nucleoprotein and hemagglutinin-neuraminidase cooperate to block secondary infection
4 affiliations
- 1College of Veterinary Medicine, Northwest A&F University
- 2Laboratory Animal Center, Xi'an Jiaotong University Health Science Center
- 3Engineering Research Center of Efficient New Vaccines for Animals, Ministry of Education
- 4Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs
Abstract
Superinfection exclusion (SIE) is a well-documented phenomenon in virology, wherein a primary viral infection prevents subsequent infection by the same or closely related viruses through various mechanisms. This phenomenon has been observed with Newcastle disease virus (NDV), a member of the Paramyxoviridae family. However, the molecular mechanisms underlying NDV-mediated SIE remain unclear. In this study, we elucidate a dual-barrier mechanism of NDV-mediated SIE, involving both the nucleoprotein (NP) and the hemagglutinin-neuraminidase (HN) glycoprotein. Our findings demonstrate that NDV SIE is initiated within 2 h of primary infection and intensifies over time, independent of viral virulence and host cell type. The NP protein forms an early cytoplasmic barrier by sequestering incoming NP subunits, while HN-neuraminidase activity at the viral membrane cleaves sialic acid receptors, preventing secondary virion adsorption. Furthermore, our data reveal that NDV-mediated SIE is specific to intraspecies interactions and does not extend to heterologous viruses, such as vesicular stomatitis virus.
IMPORTANCE: Superinfection exclusion (SIE) is a crucial viral strategy for limiting co-infection and ensuring the dominance of a single viral strain. The identification of the dual-barrier mechanism in Newcastle disease virus (NDV), involving both the nucleoprotein (NP) and hemagglutinin-neuraminidase (HN) proteins, significantly enhances our understanding of viral defense mechanisms. By elucidating how SIE operates at both the cytoplasmic and membrane levels, this study not only provides a mechanistic framework for NDV interference but also opens avenues for therapeutic applications. The discovery that NP and HN act synergistically to block secondary infection presents new strategies for combating viral co-infection in veterinary medicine and potentially in human viruses. Furthermore, understanding the viral determinants involved in SIE could guide the development of antiviral therapies that exploit these mechanisms to prevent superinfection and reduce viral spread.
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BibTeX
@article{lu2026dualbarrier,
title = {{Dual-barrier mechanism of superinfection exclusion in Newcastle disease virus: nucleoprotein and hemagglutinin-neuraminidase cooperate to block secondary infection}},
author = {Kejia Lu and Xuhong Cao and Zhengwu Chang and Xi Wei and Sa Xiao and Zengqi Yang and Haijin Liu},
journal = {mBio},
year = {2026},
month = oct,
doi = {10.1128/mbio.03545-25},
url = {https://journals.asm.org/doi/10.1128/mbio.03545-25},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dual-barrier mechanism of superinfection exclusion in Newcastle disease virus: nucleoprotein and hemagglutinin-neuraminidase cooperate to block secondary infection
AU - Kejia Lu
AU - Xuhong Cao
AU - Zhengwu Chang
AU - Xi Wei
AU - Sa Xiao
AU - Zengqi Yang
AU - Haijin Liu
PY - 2026
DA - 2026/10/14
JO - mBio
DO - 10.1128/mbio.03545-25
UR - https://journals.asm.org/doi/10.1128/mbio.03545-25
AB - Superinfection exclusion (SIE) is a well-documented phenomenon in virology, wherein a primary viral infection prevents subsequent infection by the same or closely related viruses through various mechanisms. This phenomenon has been observed with Newcastle disease virus (NDV), a member of the Paramyxoviridae family. However, the molecular mechanisms underlying NDV-mediated SIE remain unclear. In this study, we elucidate a dual-barrier mechanism of NDV-mediated SIE, involving both the nucleoprotein (NP) and the hemagglutinin-neuraminidase (HN) glycoprotein. Our findings demonstrate that NDV SIE is initiated within 2 h of primary infection and intensifies over time, independent of viral virulence and host cell type. The NP protein forms an early cytoplasmic barrier by sequestering incoming NP subunits, while HN-neuraminidase activity at the viral membrane cleaves sialic acid receptors, preventing secondary virion adsorption. Furthermore, our data reveal that NDV-mediated SIE is specific to intraspecies interactions and does not extend to heterologous viruses, such as vesicular stomatitis virus. IMPORTANCE: Superinfection exclusion (SIE) is a crucial viral strategy for limiting co-infection and ensuring the dominance of a single viral strain. The identification of the dual-barrier mechanism in Newcastle disease virus (NDV), involving both the nucleoprotein (NP) and hemagglutinin-neuraminidase (HN) proteins, significantly enhances our understanding of viral defense mechanisms. By elucidating how SIE operates at both the cytoplasmic and membrane levels, this study not only provides a mechanistic framework for NDV interference but also opens avenues for therapeutic applications. The discovery that NP and HN act synergistically to block secondary infection presents new strategies for combating viral co-infection in veterinary medicine and potentially in human viruses. Furthermore, understanding the viral determinants involved in SIE could guide the development of antiviral therapies that exploit these mechanisms to prevent superinfection and reduce viral spread.
SN - 2150-7511
ER -