Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of Aedes aegypti Mosquito Midguts

Steven M Erb; Siritorn Butrapet; John T Roehrig; Claire Y-H Huang; Carol D Blair

doi:10.3390/v14071569

Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of Aedes aegypti Mosquito Midguts

Viruses. 2022 Jul 19;14(7):1569. doi: 10.3390/v14071569.

Authors

Steven M Erb¹, Siritorn Butrapet², John T Roehrig², Claire Y-H Huang², Carol D Blair¹

Affiliations

¹ Center for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
² Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.

Abstract

Dengue viruses (DENVs), serotypes 1-4, are arthropod-borne viruses transmitted to humans by mosquitoes, primarily Aedes aegypti. The transmission cycle begins when Ae. aegypti ingest blood from a viremic human and the virus infects midgut epithelial cells. In studying viruses derived from the DENV2 infectious clone 30P-NBX, we found that when the virus was delivered to female Ae. aegypti in an infectious blood meal, the midgut infection rate (MIR) was very low. To determine if adaptive mutations in the DENV2 envelope (E) glycoprotein could be induced to increase the MIR, we serially passed 30P-NBX in Ae. aegypti midguts. After four passages, a single, non-conservative mutation in E protein domain II (DII) nucleotide position 1300 became dominant, resulting in replacement of positively-charged amino acid lysine (K) at position 122 with negatively-charged glutamic acid (E; K122E) and a significantly-enhanced MIR. Site directed mutagenesis experiments showed that reducing the positive charge of this surface-exposed region of the E protein DII correlated with improved Ae. aegypti midgut infection.

Keywords: Aedes aegypti; adaptive mutation; dengue viruses.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Aedes*
Animals
Dengue Virus* / genetics
Dengue*
Female
Humans
Serogroup

Grants and funding

This study was supported by the Centers for Disease Control and Prevention, and grants from the Pediatric Dengue Vaccine Initiative (PDVI TR-159A) and the College of Veterinary Medicine and Biomedical Sciences Research Council, Colorado State University.