Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens

Abstract

The mosquito Culex quinquefasciatus poses a substantial threat to human and veterinary health as a primary vector of West Nile virus (WNV), the filarial worm Wuchereria bancrofti, and an avian malaria parasite. Comparative phylogenomics revealed an expanded canonical C. quinquefasciatus immune gene repertoire compared with those of Aedes aegypti and Anopheles gambiae. Transcriptomic analysis of C. quinquefasciatus genes responsive to WNV, W. bancrofti, and non-native bacteria facilitated an unprecedented meta-analysis of 25 vector-pathogen interactions involving arboviruses, filarial worms, bacteria, and malaria parasites, revealing common and distinct responses to these pathogen types in three mosquito genera. Our findings provide support for the hypothesis that mosquito-borne pathogens have evolved to evade innate immune responses in three vector mosquito species of major medical importance.

Figure 1

Infection response genes (IRGs) in the mosquitoes Culex quinquefasciatus (Cq), Aedes aegypti (Aa) and Anopheles gambiae (Ag). (A) Shared and unique infection response genes in C. quinquefasciatus infected with a filarial worm, bacteria, or virus. (B) Proportions of shared and unique IRGs post-infection with viruses (1), filaria (2) or bacteria (3) in C. quinquefasciatus and A. aegypti, in C. quinquefasciatus and A. gambiae (4), and in all three species (5); and common IRGs in C. quinquefasciatus, A. aegypti, and A. gambiae (6). (C) Orthology relationships for IRG sets (Rows 1–6). IRGs with orthologs in at least 20 arthropod species were classified as Universal, as compared to Non-Universal or Mosquito-Specific. Gene copy-number counts distinguish mostly single- and multi-copy orthologous groups. IRG sets 1–6 were compared to 10,083 mosquito OGs (Row M) to identify significantly greater or smaller (asterisks) proportions (Fisher's Exact Tests: p<1e-5). (D) Consensus functional categories of universal single-copy (left) and multi-copy (right) orthologous groups of IRG sets Rows 1–6, and all mosquito groups (Row M). Functional groups are described in SOM, and (24). Each set of IRGs is described in Supplemental Tables S7–12.