Can persistent Epstein-Barr virus infection induce Chronic Fatigue Syndrome as a Pavlov reflex of the immune response?

TL;DR

This paper models how persistent Epstein-Barr virus infection could induce Chronic Fatigue Syndrome through an immune system mechanism akin to Pavlovian conditioning, using statistical mechanics and neural analogies.

Contribution

It introduces a novel theoretical framework linking persistent infection to immune system metastability and Pavlovian reflex phenomena, supported by experimental data.

Findings

Persistent infection can lead to a metastable immune state.

Immune responses can become conditioned like Pavlovian reflexes.

Experimental data support the model's predictions.

Abstract

Chronic Fatigue Syndrome is a protracted illness condition (lasting even years) appearing with strong flu symptoms and systemic defiances by the immune system. Here, by means of statistical mechanics techniques, we study the most widely accepted picture for its genesis, namely a persistent acute mononucleosis infection, and we show how such infection may drive the immune system toward an out-of-equilibrium metastable state displaying chronic activation of both humoral and cellular responses (a state of full inflammation without a direct "causes-effect" reason). By exploiting a bridge with a neural scenario, we mirror killer lymphocytes $T_K$ and $B$ cells to neurons and helper lymphocytes $T_{H_1},T_{H_2}$ to synapses, hence showing that the immune system may experience the Pavlov conditional reflex phenomenon: if the exposition to a stimulus (EBV antigens) lasts for too long, strong internal correlations among $B,T_K,T_H$ may develop ultimately resulting in a persistent activation even though the stimulus itself is removed. These outcomes are corroborated by several experimental findings.