Commensal Viruses of Mosquitoes: Host Restriction, Transmission, and Interaction with Arboviral Pathogens

Abstract

Recent advances in virus detection strategies and deep sequencing technologies have enabled the identification of a multitude of new viruses that persistently infect mosquitoes but do not infect vertebrates. These are usually referred to as insect-specific viruses (ISVs). These novel viruses have generated considerable interest in their modes of transmission, persistence in mosquito populations, the mechanisms that restrict their host range to mosquitoes, and their interactions with pathogens transmissible by the same mosquito. In this article, we discuss studies in our laboratory and others that demonstrate that many ISVs are efficiently transmitted directly from the female mosquito to their progeny via infected eggs, and, moreover, that persistent infection of mosquito cell cultures or whole mosquitoes with ISVs can restrict subsequent infection, replication, and transmission of some mosquito-borne viral pathogens. This suggests that some ISVs may act as natural regulators of arboviral transmission. We also discuss viral and host factors that may be responsible for their host restriction.

Keywords: bunyaviruses; flaviviruses; insect-specific viruses; mesoniviruses; mosquito-borne viruses; negeviruses.

Figure 1

Map of Australia showing general locations of insect-specific flavivirus isolations.

Figure 2

Bayesian phylogenies of flaviviruses over the whole open reading frame nucleotide sequence. The tree was constructed in Geneious using MrBayes v3.2.2 under the Bayesian Marko chain Monte Carlo (MCMC) model with a general time reversible substitution model, gamma distribution (five discrete gamma categories), and invariant rates among sites. Horizontal branch lengths represent posterior probabilities. The tree has been rooted using the outgroup Modoc virus (MODV), a flavivirus with no known vector. The colored nodes represent insect-specific flaviviruses (ISFs), with Lineage I in blue and Lineage II in red.

Figure 3

(A) Phylogenetic analysis of representative bunyaviruses showing the taxonomic position of goukoviruses. Maximum likelihood, midpoint rooted phylogenetic tree of Bunyavirus amino acid sequences over the complete RdRP open reading frame. The tree was constructed based on an MAFFT alignment via the CIPRES gateway and using Mega v7.0.14 tree builder with the Jones–Taylor–Thornton genetic distance model. Numbers on branches represent bootstrap values. Scale bar represents the number of substitutions per site. (B) The map shows distribution of new goukoviruses isolated in Australia and Papua New Guinea (PNG).

Figure 4

Phylogenetic tree showing the genetic relationship between the proposed species of the Mesoniviridae across the whole genome in nucleotides. The tree was constructed in Geneious using MrBayes v3.2.2 under the Bayesian Marko chain Monte Carlo (MCMC) model with a general time reversible substitution model, gamma distribution (five discrete gamma categories), and invariant rates among sites (Huelsenbeck and Ronquist, 2001). Horizontal branch lengths represent posterior probabilities. MenoV is used as an outgroup. Red text represents new Australian Alphamesonivirus-1 isolates. Scale bar represents substitutions per site.