Virus-host swinging party in the oceans: Incorporating biological complexity into paradigms of antagonistic coexistence

Abstract

Bacteria and their viruses (phages) are antagonists, yet have coexisted in nature for billions of years. Models proposed to explain the paradox of antagonistic coexistence generally reach two types of solutions: Arms race-like dynamics that lead to hosts and viruses with increasing resistance and infection ranges; and population fluctuations between diverse host and viral types due to a metabolic cost of resistance. Recently, we found that populations of the marine cyanobacterium, Prochlorococcus, consist of cells with extreme hypervariability in gene sequence and gene content in a viral susceptibility region of the genome. Furthermore, we found a novel cost of resistance where resistance to one set of viruses is accompanied by changes in infection dynamics by other viruses. In this combined mini-review and commentary paper we discuss these findings in the context of existing ecological, evolutionary and genetic models of host-virus coexistence. We suggest that this coexistence is governed mainly by fluctuations between microbial subpopulations with differing viral susceptibility regions and that these fluctuations are driven by both metabolic and enhanced infection costs of resistance. Furthermore, we suggest that enhanced infection leads to passive host-switching by viruses, preventing the development of hosts with universal resistance. These findings highlight the vital importance of community complexity for host-virus coexistence.

Figure 1. Schematic representation of bacterial population dynamics with and without enhanced infection. In this simplified depiction, a single ancestral host and 4 viruses are present. The ancestral host is susceptible to viruses A, B and D each of which infect the host with equal efficiency. This ancestral host is not initially susceptible to virus C. In the absence of enhanced infection, declines in the abundance of the host (red line) result from contact with viruses A, B and D but not with virus C and reduce the population to the same abundance. With the existence of enhanced infection, declines in the abundance of the host (blue line) result from interactions with all 4 viruses and are to different lower bounds. In this latter scenario, the mutation conferring resistance to virus A increased the infection efficiency of virus B for the emergent resistant strain, and the mutation conferring resistance to virus A or B made it susceptible to virus C. This depiction assumes that there is no growth rate cost to mutations and no virus counter-mutations occur.

Figure 2. Enhanced infection leads to shifts in the phages exerting population control. In a given environment a host population (large oval shape) encounters diverse viral types (small geometric symbols) with different capacities for infecting the host. Non-infective viruses are positioned at the top corner, viruses with high infectivity (rapid) are at the bottom left corner and viruses with low infectivity (slow) are at the bottom right corner of each infectivity triangle. Over time the host acquires mutations that change the ability of viruses to infect it, thus changing their position in the infectivity triangle. To aid traceability the color of the viruses represents their initial capacity for infection in the T₀ triangle while their position at subsequent time points (T₁ and T₂) represents their current capacity for infection. In the left panel host mutations conferring resistance to viruses are not associated with enhanced infection by other viruses and therefore viral shifts in infection capacity are unidirectional. In this case, the accumulation of resistance mutations leads to a generalist bacterium that, in the absence of a metabolic cost of resistance or a counter-mutation in the virus, would come to dominate the population. In the right panel host mutations conferring resistance to viruses are associated with enhanced infection leading to bidirectional changes in infection capabilities by other viruses. In this case, the accumulation of resistance mutations results in shifts in the viruses capable of infecting the host rather than a reduction in the number of viruses that can infect it. Therefore enhanced infection prevents a single bacterial strain from taking over the population by continuous shifts in the virus exerting control, and thus helps maintain bacterial diversity.

Figure 3. The dynamic host range of a virus. Initially (A) two virus-host pairs (V₁-H₁ and V₂-H₂) are present in a common environment, but do not cross infect each other. Following a mutation, H₁ gains resistance to V₁ giving rise to H₁^m (B). In this scenario we assume that the emergent host has no growth rate cost of resistance. Thus the population size of H₁^m will increase while that of H₁ will decline due to viral infection (depicted by a smaller circle). The survival of V₁ now depends on its ability to gain a new host. To keep up in an arms race (C) a counter-mutation in V₁ gives rise to a host range mutant (V₁^m) which can reinfect H₁^m, thereby enabling the recoupling of the virus-host pair. Alternatively, passive host switching occurs through enhanced infection (D), whereby V₁ is provided with a new host (H₂^m) due to a mutation in H₂ that conferred resistance to, and was selected by, another virus, V₂ (D). Thus an independent interaction between H₂ and V₂ provided the V₁ population with another host without any mutation in V₁. In summation, the arms race and enhanced infection lead to a dynamic host range for V₁. Despite the fact that this virus lost its immediate host (H₁) through a resistance mutation, its host range can be considered to include both H₁^m and H₂. These bacterial types are only one mutation away from serving as its immediate hosts, as a single mutation in these bacteria or in V₁ can lead to productive infection.