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Publications

Journal Article Ahead of print

PubMed: 42320843 DOI: 10.1016/j.ijid.2026.108894

Genomic conservation and CNS-associated intra-host variation of Nipah virus during the 1998-1999 Malaysian outbreak.

Int J Infect Dis

Authors: Heng Choon Cheong, Foo Hou Tan, Hui Ming Ong, Kum Thong Wong, Kien Chai Ong, Soon Hao Tan, Chong Tin Tan, Li Ping Wong, Jie Ping Schee, Rozainanee Mohd-Zain, Aziyah Mat Rahim, Nuryana Idris, Kok Keng Tee, Li-Yen Chang

Affiliations

  • Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
  • Department of Pathology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
  • Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
  • Department of Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
  • Center for Population Health (CePH), Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian, China; Department of Medicine, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
  • Virology Unit, Infectious Disease Research Centre (IDRC), Institute for Medical Research (IMR), National Institute of Health (NIH), Bandar Setia Alam, 40170 Shah Alam, Selangor, Malaysia.
  • School of Public Health, Kunming Medical University, Kunming, Yunnan 650500, China.
  • Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; Malaysian Genome and Vaccine Institute, Jalan Bangi, 43000 Kajang, Selangor, Malaysia.

Abstract

OBJECTIVES

Nipah virus (NiV) is a highly pathogenic henipavirus responsible for recurrent outbreaks of severe encephalitis. This study aimed to address gaps in historical genomic data by characterizing NiV genomes recovered from archived central nervous system (CNS) tissues from the 1998-1999 Malaysian outbreak and evaluating viral evolution and intra-host genetic variation.

METHODS

We analyzed 18 NiV genomes obtained from archived CNS tissues. Whole-genome sequencing was performed, followed by phylogenetic reconstruction, comparative genomic analysis, and intra-host single nucleotide variant (iSNV) profiling. Paired CNS tissue samples from the individual patients were included to assess regional viral heterogeneity across distinct CNS tissues.

RESULTS

All Malaysian NiV sequences formed a highly conserved, monophyletic clade (NiV-MY), distinct from the Bangladesh-India lineage (NiV-BD). Overall genomic diversity was low, with high amino acid conservation across the genome. Although intra-host variation was limited, however, paired CNS tissue samples from two patients contained closely related but non-identical genomes, differing by a single nucleotide in the attachment glycoprotein (G) gene, indicating localized genetic variation across distinct CNS tissues.

CONCLUSIONS

NiV from the Malaysian outbreak demonstrated remarkable genomic conservation consistent with a single dominant introduction or a highly restricted set of closely related introductions. Nevertheless, the presence of limited intra-host variation highlights ongoing micro-evolution within the CNS and underscores the importance of continued genomic surveillance to better understand NiV evolutionary dynamics.

MeSH

Genetic Variation, Genes, Quasispecies, Genome, Central Nervous System, Nipah Virus, Viruses, Tissues, Communicable Diseases, Henipavirus