Abstract
INTRODUCTION: Human adenovirus infections are typically associated with acute respiratory infection, keratoconjunctivitis, acute cystitis, hepatitis, and gastroenteritis, while central nervous system (CNS) related infections are rarely reported. METHODS: In this study, a novel human adenovirus was identified in the cerebrospinal fluid from an encephalitis patient with X-linked agammaglobulinemia via metagenomic next-generation sequencing (mNGS). Probe capture enrichment sequencing and PCR validation further confirmed the presence of this adenovirus in the patient's cerebrospinal fluid. RESULTS: Whole-genome analysis classified the virus within the Human mastadenovirus D species, revealing an approximately 2000 bp deletion in the E3 gene that resulted in the loss of CR1-gamma and RID-alpha regions and the formation of a novel open reading frame (ORF). The penton base, hexon, and fiber genes were identified as P33H28F71, designating this virus as a novel type, subsequently named HAdV-D116 by the Human Adenovirus Working Group. Recombination analysis suggested that HAdV-D116 is a recombinant strain derived from HAdV-D33, HAdV-D28, and HAdV-D71. Structural analysis of the fiber-knob domain indicated that HAdV-D116 likely uses sialic acid as a receptor. DISCUSSION: The unique genomic features of HAdV-D116, combined with the patient's immunodeficiency, are proposed to contribute to its possible CNS infectivity. The discovery of HAdV-D116 expands our understanding of human adenovirus tropism and underscores the need for vigilance regarding the emergence of novel adenovirus-related CNS infections.