Clearance of anogenital and oropharyngeal HPV infections is attributed primarily to a successful adaptive immune response .

In particular, we find that in immunocompetent adolescents with cervical HPV infections, the immune response may contribute less than 20% to virus clearance—the rest is taken care of by the stochastic proliferation dynamics in the basal layer.

In HIV-negative individuals, the contribution of the immune response may be negligible.

Clearance of HPV infection is usually attributed to an effective immune response , and the observation of longer clearance times in immunocompromised individuals further corroborates this assumption [9].

On the other hand, the fact that development of antibodies preventing future reinfection after clearing of the virus (known as seroconversion) occurs only partially [10—14] suggests that mechanisms other than an effective immune response may contribute to viral clearance.

Immune response .

Even though HPV is equipped with molecular mechanisms that facilitate immune evasion after infection, it is generally assumed that clearance of the Virus is the result of a successful immune response [25, 33].

Initially, detection of the infection triggers an innate immune response which targets the Virions that are released at the surface, as well as infected cells in the superficial layers.

Stochasticity vs immune response

In particular, the coexistence of preexisting and mutated strains triggers a heightened immune response due to the larger total pathogen population; this feedback can smother mutated strains before they reach an ample size and establish.

This evolution can either result in the production of neW pathogens, or neW strains of existing pathogens that escape prevailing drug treatments or immune responses .

Specifically, once a mutated pathogen arises that spreads more quickly than the initial (resident) strain, it potentially triggers a heightened immune response that can eliminate the mutated strain before it spreads.

Parasite and pathogen evolution can radically affect the course of infections in hosts able to mount immune responses .

All these scenarios can be analysed in the larger framework of evolutionary rescue [18, 19] , where a change in the environment (in this case, the activation of an immune response ) will cause the population to go extinct unless it evolves (develops an increased replicative ability, then subsequently rise to a large enough size to avoid stochastic loss).

This effect can be exacerbated by the fact that the mutated strain also prompts an increased immune response , so the emerging infection has a stronger defence to initially compete with (assuming immune growth is proportional to the total size of the pathogen population).

(P1, (P2 Growth rate of initial, mutated infection x1, x2 Size of initial, mutated infection y Size of immune response

K Maximum size of immune response r Unscaled growth rate of immune response

Table 4 shows that these interaction modules were associated with biological processes related to ligase activity, ubiquitination, protein modification, transcription and translation, immune response , signaling, cytoskeleton organization, development, and mRNA processing.

For example, the interaction modules allowed us to identify a biological process termed “pos-itive regulation of protein ubiquitination” instead of just “protein ubiquitination.” Importantly, the analysis provided evidence of a much larger effort to target intracellular host signaling processes, in particular those related to the immune response .

Each of the interaction modules constituting ubiquitination and ligase activity, transcriptional regulation, immune response , cy-toskeleton organization, and mRNA processing, consisted of proteins and interactions that were closely grouped together in the largest connected component (Fig.

Here, we performed a systematic analysis of these interactions to investigate the mechanisms by which B. mallei virulence factors interact with host proteins to establish infection, evade host immune responses , and spread within the host.

Analyses of these host-pathogen PPI datasets showed that virulence-associated pathogen proteins preferentially target host proteins involved in biological processes essential for cell vitality, e.g., signaling, cell cycle, or immune response [9—13].