Emergence, surge, and fading of the novel feline parvovirus Thr390Ala mutant in Egyptian cats during 2023: insights from a comprehensive full-length VP2 genetic analysis.

Abstract

BACKGROUND: Feline parvovirus (FPV) causes feline panleukopenia (FPL) and cerebellar ataxia (CA) in cats. to date, only two complete Egyptian VP2 sequences have been available in GenBank. To investigate FPV diversity And evolution in Egypt, we generated 24 complete VP2 sequences from diseased cats during two FPV activity peaks in 2023 (January-February and November-December). Egyptian sequences were Analyzed with 967 global references to assess selection pressure and phylogenetic relationships. In silico predictions of VP2 Antigenic sites, 3D structure, and phosphorylation potential were performed to evaluate the impact of identified mutations. RESULTS: Egyptian sequences showed 99.3-100% nt And 99.8-100% aa identity among themselves, And 98.6-100% nt And 98.4-100% aa identity with global references. The overall dN/dS ratio was 0.121, with codon 101 under positive selection. Compared to the prototype FPV-b strain (M38246), Egyptian strains had 32 mutations (3 nonsynonymous: Ala5Thr, Ile101Thr, and Thr390Ala; 29 synonymous), forming 19 nt And 3 aa sequence types. Notably, Thr390Ala was unique to Egyptian sequences and absent from all global references. Phylogenetically, Egyptian strains formed two subclades: one composed solely of sequences carrying Thr390Ala (n = 13), And Another including the remaining 11 sequences clustering with 19 global strains sharing the synonymous mutation C135T in addition to A927G and/or A1236G. The Thr390Ala variant predominated in the first peak (11/17, 64.7%) but declined in the second (2/7, 28.6%). Residue 390 lies within an epitope-rich region (aa 350-450) and was predicted to be a phosphorylation site. Thr390Ala caused a modest drop in epitope score, disrupted local hydrogen bonding, and abolished predicted phosphorylation. CONCLUSIONS: Beyond expanding the global dataset with the largest number of Egyptian full-length VP2 sequences to date, this study highlights the Thr390Ala mutant as a classic example of evolutionary trade-off: it emerged and predominate during the first peak, potentially as an immune escape variant, but declined in the second peak, likely due to structural constraints and competition with fitter variants. Despite strong purifying selection, this case illustrates that FPV evolution is not entirely static. This underscores the need for continuous genetic monitoring to capture viral evolution in real time and inform effective control strategies.