Speaker
Description
Social microbial behavior has been recognized as a contributor to clinical challenges such as antibiotic resistance and immune evasion. In structured communities, like bacterial biofilms, cooperation among specialized subpopulations ensures survival. Growing evidence suggests social interactions may also influence viral adaptation. For example, hepatitis C virus (HCV) is hypothesized to exhibit antigenic cooperation, wherein altruistic variants act to divert immune responses, enabling the immune escape of persistent variants. This raises the question: can chronic viral infections be better understood through a social framework? Cooperative behavioral dynamics within measurably evolving populations such as bacteria and viruses can be disrupted by mutation, often requiring compensatory mutations (i.e., co-evolution) to restore function and subpopulation homeostasis. Human immunodeficiency virus (HIV) is one of the most rapidly mutating infectious viruses, suggesting occurrences of compensatory mutations within the host may occur with sufficient frequency to detect the presence of cooperative behavior and inform the interactions responsible. Yet, no computational tool exists that can distinguish population-level from individual genome co-evolution. To address this, we developed a phylogeny-based Bayesian graphical model capable of capturing significantly co-evolving sites within simulated viral populations with 96% accuracy. We applied this tool to HIV envelope sequences sampled longitudinally from multiple tissues within 12 S[imian]IV-infected macaques. Four co-evolving amino acid sites were shared among 11 of the animals, indicating similar selective pressures for interacting genetic regions across hosts. Three of these sites were located in variable regions V1-V3, where mutations have been previously implicated in evading antiretroviral and immune responses. Taken together, these findings suggest the previously painted picture of immune selection pressure on individual variants may not be sufficient to explain viral adaptation to the host’s immune system and that co-evolution of these sites may be required for a cooperative mechanism of immune evasion.
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