Adaptation of HIV-1 Depends on the Host-Cell Environment

Many viruses have the ability to rapidly develop resistance against antiviral drugs and escape from the host immune system. To which extent the host environment affects this adaptive potential of viruses is largely unknown. Here we show that for HIV-1, the host-cell environment is key to the adaptive potential of the virus. We performed a large-scale selection experiment with two HIV-1 strains in two different T-cell lines (MT4 and C8166). Over 110 days of culture, both virus strains adapted rapidly to the MT4 T-cell line. In contrast, when cultured on the C8166 T-cell line, the same strains did not show any increase in fitness. By sequence analyses and infections with viruses expressing either yellow or cyan fluorescent protein, we were able to show that the absence of adaptation was linked to a lower recombination rate in the C8166 T-cell line. Our findings suggest that if we can manipulate the host-cellular factors that mediate viral evolution, we may be able to significantly retard viral adaptability

Effects of Random Mutations in the Human Immunodeficiency Virus Type 1 Transcriptional Promoter on Viral Fitness in Different Host Cell Environments

A mutation's effect on fitness or phenotype may in part depend on the interaction of the mutation with the environment. The resulting phenotype or fitness is important, since it determines the adaptive potential of a species. To date, most studies have focused on alterations to protein-coding regions of the genome and their consequential fitness effects. Non-protein-coding regulatory regions have been largely neglected, although they make up a large and important part of an organism's genome. Here, we use human immunodeficiency virus type 1 as a model system to investigate fitness effects of random mutations in noncoding DNA-binding sites of the transcriptional promoter. We determined 242 fitness values for 35 viral promoter mutants with one, two, or three mutations across seven distinct cellular environments and identified that (i) all mutants have an effect in at least one cellular environment; (ii) fitness effects are highly dependent on the cellular environment; (iii) disadvantageous and advantageous mutations occur at high and similar frequencies; and (iv) epistatic effects of multiple mutations are rare. Our results underline the evolutionary potential of regulatory regions and indicate that DNA-binding sites evolve under strong selection, while at the same time, they are very plastic to environmental change

Catastrophic collapse can occur without early warning: examples of silent catastrophes in structured ecological models.

Catastrophic and sudden collapses of ecosystems are sometimes preceded by early warning signals that potentially could be used to predict and prevent a forthcoming catastrophe. Universality of these early warning signals has been proposed, but no formal proof has been provided. Here, we show that in relatively simple ecological models the most commonly used early warning signals for a catastrophic collapse can be silent. We underpin the mathematical reason for this phenomenon, which involves the direction of the eigenvectors of the system. Our results demonstrate that claims on the universality of early warning signals are not correct, and that catastrophic collapses can occur without prior warning. In order to correctly predict a collapse and determine whether early warning signals precede the collapse, detailed knowledge of the mathematical structure of the approaching bifurcation is necessary. Unfortunately, such knowledge is often only obtained after the collapse has already occurred

The disease can facilitate the predator, relieve stuntedness and induce recurrent epidemics.

<p>Parameters and colors are identical to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132251#pone.0132251.g002" target="_blank">Fig 2</a>, except δ = 0, indicating that sick individuals do not effectively compete with healthy individuals. <i>(a)</i> Dynamics after introduction of the disease in the stunted population state for <i>μ</i>_<i>P</i>. = 0.45. Here, the disease causes a single epidemic, after which the host population shifts to the non-stunted equilibrium and the disease goes extinct. <i>(b)</i> Dynamics after introduction of the disease in the stunted population state for <i>μ</i>_<i>P</i>. = 0.56. After an initial large epidemic, the system settles in a limit cycle with recurrent epidemics of intermediate amplitude. Note that each epidemic is closely followed by an increase in predator density. <i>(c)</i> Bifurcation diagram for total juvenile prey density as a function of predator death rate <i>μ</i>_<i>P</i>. The solid blue line indicates the stable disease free state, and the solid purple line denotes the endemic state. The red lines and area indicate the amplitude of the stable limit cycles. Dashed lines are unstable equilibriums.</p

Equal Pay for all Prisoners / The Logic of Contrition

This report deals with two questions concerning the emergence of cooperative strategies in repeated games. The first part is concerned with the Perfect Folk Theorem and presents a vast class of equilibrium solutions based on Markovian strategies. Simple strategies, called equalizers, are introduced and discussed: if players adopt such strategies, the same payo# results for every opponent. The second part analyzes strategies implemented by finite automata. Such strategies are relevant in an evolutionary context; an important instance is called Contrite Tit For Tat. In populations of players adopting such strategies, Contrite Tit For Tat survives very well---at least as long as errors are restricted to mistakes in implementation (&apos;the trembling hand&apos;). However, this cooperative strategy cannot persist if mistakes in perception are included as well. --iv-- About the Authors Maarten Boerlijst Department of Zoology University of Oxford South Parks Road Oxford OX1 3PS, UK Martin Nowak Depa..