May viral (antigen) load be the real crucial tool leading to anergy in a "micro-evolutionary" model of host/virus...

The hypothesis in the present work is that in host/virus/tumor (antigens) interactions, leading to anergy of the immune system, the Viral (antigen) load plays a crucial and central role, which all interactions turn around.

Notwithstanding apparent strong favorable evidences, the still prevailing concept of "active virus strategies to escape" may be misleading, since it might hide the cited pivotal role in a wide number of researches. This concept could be easily substituted by a microevolutionary model explaining many unresolved questions and allowing to emerge the role of antigen load conditioned reactions of the host's immune system as motivated choices. EVIDENCES: An anergy induced condition can be detected not only in HCV, but also in the course of persistent viral (e.g. HBV, HIV) and non viral parasitic infections (e.g. Leishmania and Helminths) which share the same host's reactions leading to anergy, independently on the infecting agents. The starting point of those reactions is always time elapsing from the primary infection after a short early (often undetected) period of high viral(antigen) load in the lack of clearance. This latter seems then the only conceivable link between such so different infections determining, as far as HBV and HCV are concerned, also Hepatocarcinoma under indirect facilitating conditions. In a wide majority of studies it seems clearly evident that viral load exerts a main role which contributes to determine host chosen reactions aimed at avoiding dangerous outcomes while controlling viral load. Strong clinical (i.e. both HIV infected patients treated with HAART, and helminths infected people with deworming drugs acting directly on viral and parasitic loads) and experimental studies (i.e. chimpanzees (the only animal model of HCV infection) infected with HBV inocula of different size) are here reported or cited to highlight the crucial role of antigen load also on HIV infection transmission, seroconversion, disease progression, treatment initiation and efficacy.

The new era for antiviral drugs like protease and polymerase inhibitors that seem to be more efficacious and less toxic than Ribavirin, may open the possibility to verify, when administered during the early phase of HCV infection (eventually helped by an immune-stimulant cytokine as IL-2), whether a precocious significant reduction of viral load (threshold) may allow the host to sustain his strong reactions and clear the virus within the due time, confirming the hypothesis about the crucial role of this tool which may be extended to all the cited infections.