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Viruses Might Constructively Contribute to Host Evolution

The damage and disease that viruses can inflict reinforces a belief that they tend to play negative roles during host evolution. However, persistent, if sometimes unapparent, viruses may also contribute constructively during host evolution. For instance, consider two major discontinuities that mark the evolution of organisms: the appearance of (1) the eukaryotic replication system and (2) live (viviparous) birth in mammals. The interplay between genomic DNA and persistent retroviruses might have contributed to these two major evolutionary discontinuities.

Viruses and Acute Disease

Viruses can replicate exponentially in host cells, giving rise to disease symptoms and sometimes causing lethal damage. Two of my students, Victor Defillipis and Keith Gottlieb, and I call this type of viral activity "acute replication." In some cases it is also characterized by very high rates of genetic variation, leading to quasispecies of virus in which certain viral populations evolve at rates up to 1-million-fold greater than that of their respective hosts. Acute viral agents, such as influenza A and smallpox virus, can cause epidemic disease but require large or congregational host populations.

Such viruses tend not to persist within individual hosts. Furthermore, many viruses can tolerate minor genetic defects and errors in replication far better than can their hosts. For instance, viral populations may accumulate many defects, making their overall infectious efficiency rather poor, with particle to plaque-forming-unit (PFU) ratios of 100-1,000 being fairly common. Human immunodeficiency virus (HIV) is particularly notorious for its error-prone replication. According to current estimates, each round of HIV-1 replication in a single cell leads to 1 in 10,000 viral genomes that differs in primary sequence from the parent.

Defective viruses, which are parasitic to infectious viruses, are also common. Typically such "defectives" are missing some viral sequences yet remain capable of replicating. In some cases, viral populations consisting of mixed quasispecies have greater relative fitness than do more homogeneous populations. These high rates of genetic change make such viruses phylogenetically incongruent with hosts whose own genomes are only slowly changing. Thus, acute-replicating viruses sometimes need to find new, uninfected hosts during the transiently productive period of host infection. The relative fitness of acute viral agents along with virus-host dynamics can be described mathematically in terms of the basic replicative rate (a dimensionless ratio of parent virus to successful offspring) and a predator-prey relationship.

Persistent Inapparent Virus

In contrast to acute-replicating viruses, some viruses persist in their hosts, following an "alternative persistent life strategy," in which a virus remains within an individual host following initial infection, retaining its capacity for renewed or episodic reactivated replication and eventual transmission to a new host. This pattern is common to many DNA-containing viruses and RNA-containing retroviruses, including human herpesviruses, Epstein-Barr virus, adenovirus, papillomaviruses, TT virus, and polyomaviruses. Many RNA viruses, such as hantavirus in rodent hosts or influenza virus in waterfowl, can also persist in genetically stable forms despite high error rates associated with viral RNA polymerase.

The general characteristics of persistent infections include high prevalence in a specific host, lifelong infections, few or no overt disease symptoms (seemingly commensal), both noncongregational and congregational hosts, genetic stability, and phylogenetic congruence with hosts. These viral lineages also tend to be very old and monophyletic. However, these persistent viruses are not the same as selfish DNA in that such viruses need a clear phenotype to assure persistence, reactivation, and transmission.

The mechanisms that enable eukaryotic viruses to persist, however, are poorly characterized, and there are no rigorous mathematical models to describe their relative fitness or population dynamics. However, their basic behavior indicates that maximizing replication is not the single determinant of relative fitness. Instead, an additional temporal component is certainly essential. For example, an individual human infected with herpes zoster during childhood may spend the next 50 years not producing any virus. Yet, the few viral genomes that persist in ganglions maintain fitness and retain their capacity to reactivate and to transmit the infection to other hosts. In any case, persistence does not maximize replication of progeny virions, but increases the probability that new hosts will also become persistently infected at an optimal time, sometimes with a low number of highly successful viral genomes.

Genomic sequence data indicate that viruses with either persistent or acute life strategies differ in terms of their characteristic host relationships. Organisms typically have specific nucleotide word biases or signature frequencies. For instance, persisting—but not acute—viruses reflect the word bias of their host genomes. Persisting viruses thus appear to be in the same gene pool as their hosts.

Luis P. Villarreal