@article{fdi:010083145,
  title = {{E}pisome partitioning and symmetric cell divisions : quantifying the role of random events in the persistence of {HPV} infections},
  author = {{B}eneteau, {T}. and {S}elinger, {C}hristian and {S}ofonea, {M}. {T}. and {A}lizon, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{H}uman {P}apillomaviruses ({HPV}) are one of the most prevalent sexually transmitted infections ({STI}) and the most oncogenic viruses known to humans. {T}he vast majority of {HPV} infections clear in less than 3 years, but the underlying mechanisms, especially the involvement of the immune response, are still poorly known. {B}uilding on earlier work stressing the importance of randomness in the type of cell divisions in the clearance of {HPV} infection, we develop a stochastic mathematical model of {HPV} dynamics that combines the previous aspect with an explicit description of the intracellular level. {W}e show that the random partitioning of virus episomes upon stem cell division and the occurrence of symmetric divisions dramatically affect viral persistence. {T}hese results call for more detailed within-host studies to better understand the relative importance of stochasticity and immunity in {HPV} infection clearance. {A}uthor summary {E}very year, infections by {H}uman {P}apillomaviruses ({HPV}) are responsible for a large share of infectious cancers. {T}he prevalence of {HPV}s is very high, which makes it a major public health issue. {F}ortunately, most {HPV} infections (80 to 90%) are cleared naturally within three years. {A}mong the few that persist into chronic infections, the majority (88%) also regress. {H}ence for a given {HPV} infection, the risk of progression towards cancerous status is low. {T}he immune response is often invoked to explain {HPV} clearance in non-persisting infections, but many uncertainties remain. {B}esides immunity, randomness was also suggested to play an important role. {H}ere, we examine how random events occurring during the life cycle of the virus could alter the persistence of the virus inside the host. {W}e develop a mechanistic model that explicitly follows the dynamic of viral copies inside host cells, as well as the dynamics of the epithelium. {I}n our model, infection extinction occurs when all viral copies end up in differentiated cells and migrate towards the surface. {T}his can happen upon cell division during the random allocation of the episomes (e.g. independent circular {DNA} copies of the viral genome) or when a stem cell divides symmetrically to generate two differentiated cells. {W}e find that the combination of these random events drastically affects infection persistence. {M}ore generally, the importance of these random fluctuations could match that of immunity and call for further studies at the within-host and the epidemiological level.},
  keywords = {},
  booktitle = {},
  journal = {{PL}o{S} {C}omputational {B}iology},
  volume = {17},
  numero = {9},
  pages = {[16 ]},
  ISSN = {1553-734{X}},
  year = {2021},
  DOI = {10.1371/journal.pcbi.1009352},
  URL = {https://www.documentation.ird.fr/hor/fdi:010083145},
}