Evolution and ecology of influenza A viruses.

SUMMARY Coinfections involving viruses are being recognized to influence the disease pattern that occurs relative to that with single infection. Classically, we usually think of a clinical syndrome as the consequence of infection by a single virus that is isolated from clinical specimens. However, this biased laboratory approach omits detection of additional agents that could be contributing to the clinical outcome, including novel agents not usually considered pathogens. The presence of an additional agent may also interfere with the targeted isolation of a known virus. Viral interference, a phenomenon where one virus competitively suppresses replication of other coinfecting viruses, is the most common outcome of viral coinfections. In addition, coinfections can modulate virus virulence and cell death, thereby altering disease severity and epidemiology. Immunity to primary virus infection can also modulate immune responses to subsequent secondary infections. In this review, various virological mechanisms that determine viral persistence/exclusion during coinfections are discussed, and insights into the isolation/detection of multiple viruses are provided. We also discuss features of heterologous infections that impact the pattern of immune responsiveness that develops.

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Virological and Immunological Outcomes of Coinfections

Influenza virus was the first virus for which defective-interfering particles were reported. Von Magnus (1947) observed that when he passaged influenza viruses serially undiluted in embryonated chicken eggs, both the amount of total virus particles as assayed by hemagglutinating units (HAU) and the amount of infectious virus particles as assayed by egg infectivity titer (EID50) decreased. However, he observed that the proportion of infectious particles as assayed by EID50 decreased precipitously when compared to the total virus particle (HAU) production. During the undiluted passages many particles were produced which were noninfectious. These noninfectious influenza virus particles produced at high multiplicity were called “incomplete” particles. Von Magnus (1951 a–c) also described the phenomenon of interference when he reported that these “incomplete” particles interfered with the multiplication of complete (infectious, nondefective, or standard) virus particles. This phenomenon of multiplicity dependent production of noninfectious virus particles is also called the “von Magnus phenomenon.” Since this observation was made with influenza viruses, similar multiplicity-dependent formation of noninfectious particles has been observed with almost all animal viruses carefully studied to date; indeed, formation of such particles has also been reported for plant, yeast, and bacterial viruses (Kane et al. 1979; Mills et al. 1967) and, thus, probably represents a general phenomenon for all viruses. The term “defective-interfering” (DI) particles was introduced by Huang and Baltimore (1970) to describe the definitive characteristics of these noninfectious particles and to separate them from other noninfectious particles which may be noninterfering.

Defective-interfering (DI) RNAs of influenza viruses: origin, structure, expression, and interference.

Effect of antioxidants on apoptosis induced by influenza virus infection: inhibition of viral gene replication and transcription with pyrrolidine dithiocarbamate.

https://mmbr.asm.org/content/mmbr/51/2/179.full.pdf

Diana D. Huang

Papers

Persistent infection with influenza A virus: Evolution of virus mutants