A Virus Is a Community: Diversity within Negative-Sense RNA Virus Populations

Abstract

Negative-sense RNA virus populations are composed of diverse viral components that interact to form a community and shape the outcome of virus infections. At the genomic level, RNA virus populations consist not only of a homogeneous population of standard viral genomes but also of an extremely large number of genome variants, termed viral quasispecies, and nonstandard viral genomes, which include copy-back viral genomes, deletion viral genomes, mini viral RNAs, and hypermutated RNAs. At the particle level, RNA virus populations are composed of pleomorphic particles, particles missing or having additional genomes, and single particles or particle aggregates. As we continue discovering more about the components of negative-sense RNA virus populations and their crucial functions during virus infection, it will become more important to study RNA virus populations as a whole rather than their individual parts. In this review, we will discuss what is known about the components of negative-sense RNA virus communities, speculate how the components of the virus community interact, and summarize what vaccines and antiviral therapies are being currently developed to target or harness these components.

Keywords: antiviral immunity; copy-back viral genomes; copy-backs; deletion viral genomes; filamentous particles; multiple genome packaging; negative-sense RNA virus; nonstandard viral genomes; semi-infectious particles; viral quasispecies; virion aggregation; virus; virus community.

FIG 1

Functions of diverse viral genomes found in negative-sense RNA virus populations. Overview of the known effects of quasispecies and nonstandard viral genomes, such as copy-back viral genomes, deletion viral genomes, mini viral RNAs, and hypermutated RNAs, on the standard virus, host cells, and pathogenesis.

FIG 2

Functions of diverse particles found in negative-sense RNA virus populations. Overview of the known effects of filamentous particles, semi-infectious particles, multiple-genome packaging, and particle aggregation on the virus population.

FIG 3

Viral particles and viral genomes found in negative-sense RNA virus populations. On top, outside the cell, all types of viral particles discussed in the review are represented. At the bottom, within the cells, all types of viral RNAs discussed in the review are represented. The stars represent point mutations. The beginning and end structures of viral RNAs represent 3′ and 5′ sequences, respectively. Mini viral RNAs have very long deleted sequences and hence are similar to deletion viral genomes but smaller. As mini viral RNAs have only been found in IAV infections, we represented it as a hairpin loop, as IAV 3′ and 5′ ends are complementary in IAV.