Ancient and dominant: a novel feline immunodeficiency virus subtype “X-EGY” identified in Egyptian cats associated with high prevalence

Abstract

Data on the epidemiology and molecular characterization of feline immunodeficiency virus (FIV) in Egypt are limited. This study aimed to estimate FIV prevalence in 240 Egyptian cats during 2022–2024 using three diagnostic techniques: two point-of-care antibody detection kits (Anigen® and SNAP®) and one end-point PCR targeting the env gene. FIV infection is defined as positivity in at least two of the three diagnostic methods or PCR alone confirmed by sequencing, Additionally, FIV-associated clinicopathological abnormalities were assessed, and, for the first time in Egypt, circulating FIV subtypes were identified through partial sequencing and phylogenetic analysis of all env gene-positive samples (n = 10), along with 4 additional gag gene-positive samples. Using our diagnostic criteria, 76 of 240 cats (31.7%) were identified as FIV-infected. Of these 76 cases, 75 were positive on both rapid kits, yielding a sensitivity of 98.7% for sequential testing with Anigen® and SNAP®, whereas only 10 were positive on PCR and sequencing (13.2% sensitivity). FIV-infected cats exhibited lymphopenia, thrombocytosis, hyperglobulinemia, and reduced albumin/globulin ratios. On env and gag gene-based phylogenetic analyses, Egyptian strains did not cluster with any known FIV subtype (A-F and U-NZenv) but formed a distinct, previously uncharacterized clade. The Egyptian env sequences displayed low intra-group diversity (2.8–3.7%) but high divergence from all known subtypes (21–25%), with no evidence of recombination observed. Moreover, these env sequences were derived from both shelter-housed and client-owned cats across three Egyptian governorates within a one-year period. Given their genetic distinctiveness and widespread detection, we propose a novel FIV subtype, tentatively designated “X-EGY.” Its dominance and limited variability among its strains suggest it represents an ancient lineage uniquely adapted to Egyptian cats, rather than a recently emerged variant. This subtype may partly contribute to Egypt’s notably high FIV prevalence. Serological testing, utilizing two point-of-care kits in screening and confirmation steps, is the most accurate FIV diagnostic approach, outperforming molecular testing, particularly in regions where genetic data on circulating strains are scarce. Overall, the findings enhance our understanding of FIV epidemiology and diagnostic strategies and offer new insights into viral diversity and evolution.