Abstract

RNA viruses typically occur in genetically diverse populations due to their error-prone genome replication. Genetic diversity is thought to be important in allowing RNA viruses to explore sequence space, facilitating adaptation to changing environments and hosts. Some arboviruses that infect both a mosquito vector and a mammalian host are known to experience population bottlenecks in their vectors, which may constrain their genetic diversity and could potentially lead to extinction events via Muller's ratchet. To examine this potential challenge of bottlenecks for arbovirus perpetuation, we studied Venezuelan equine encephalitis virus (VEEV) enzootic subtype IE and its natural vector Culex (Melanoconion) taeniopus, as an example of a virus-vector interaction with a long evolutionary history. Using a mixture of marked VEEV clones to infect C. taeniopus and real-time RT-PCR to track these clones during mosquito infection and dissemination, we observed severe bottleneck events that resulted in a significant drop in the number of clones present. At higher initial doses, the midgut was readily infected and there was a severe bottleneck at the midgut escape. Following a lower initial dose, the major bottleneck occurred at initial midgut infection. A second, less severe bottleneck was identified at the salivary gland infection stage following intrathoracic inoculation. Our results suggest that VEEV consistently encounters bottlenecks during infection, dissemination and transmission by its natural enzootic vector. The potential impacts of these bottlenecks on viral fitness and transmission, and the viral mechanisms that prevent genetic drift leading to extinction, deserve further study.

Highlights

  • RNA virus replication is characterized by a high frequency of mutation, which leads to genetically diverse populations

  • The within-population diversity of RNA viruses is a by-product of their viral RNA-dependent RNA-polymerases (RdRp), as most viruses lack a proofreading domain in this enzyme

  • The ability of arboviruses to perpetuate in nature given that they must infect two disparate hosts remains a mystery

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Summary

Introduction

RNA virus replication is characterized by a high frequency of mutation, which leads to genetically diverse populations. This diversity is thought to enable RNA viruses to effectively survive within the host (i.e. escape or evade immune responses), to be transmitted, and to potentially adapt to new hosts or vectors. The within-population diversity of RNA viruses is a by-product of their viral RNA-dependent RNA-polymerases (RdRp), as most viruses lack a proofreading domain in this enzyme This low fidelity leads to a high error frequency for replication of all RNA viruses, which varies between 1023 and 1025 mis-incorporations per nucleotide copied. The limited oral susceptibility of many mosquito vectors to arboviruses (arthropod-borne viruses) may cause bottlenecks at the stage of initial midgut infection during natural transmission cycles

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