Publications des scientifiques de l'IRD

Beneteau T., Selinger Christian, Sofonea M. T., Alizon S. (2021). Episome partitioning and symmetric cell divisions : quantifying the role of random events in the persistence of HPV infections. PLoS Computational Biology, 17 (9), [16 p.]. ISSN 1553-734X.

Titre du document
Episome partitioning and symmetric cell divisions : quantifying the role of random events in the persistence of HPV infections
Année de publication
2021
Type de document
Article référencé dans le Web of Science WOS:000697187000010
Auteurs
Beneteau T., Selinger Christian, Sofonea M. T., Alizon S.
Source
PLoS Computational Biology, 2021, 17 (9), [16 p.] ISSN 1553-734X
Human Papillomaviruses (HPV) are one of the most prevalent sexually transmitted infections (STI) and the most oncogenic viruses known to humans. The 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. Building 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. We show that the random partitioning of virus episomes upon stem cell division and the occurrence of symmetric divisions dramatically affect viral persistence. These results call for more detailed within-host studies to better understand the relative importance of stochasticity and immunity in HPV infection clearance. Author summary Every year, infections by Human Papillomaviruses (HPV) are responsible for a large share of infectious cancers. The prevalence of HPVs is very high, which makes it a major public health issue. Fortunately, most HPV infections (80 to 90%) are cleared naturally within three years. Among the few that persist into chronic infections, the majority (88%) also regress. Hence for a given HPV infection, the risk of progression towards cancerous status is low. The immune response is often invoked to explain HPV clearance in non-persisting infections, but many uncertainties remain. Besides immunity, randomness was also suggested to play an important role. Here, we examine how random events occurring during the life cycle of the virus could alter the persistence of the virus inside the host. We develop a mechanistic model that explicitly follows the dynamic of viral copies inside host cells, as well as the dynamics of the epithelium. In our model, infection extinction occurs when all viral copies end up in differentiated cells and migrate towards the surface. This 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. We find that the combination of these random events drastically affects infection persistence. More 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.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020] ; Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010083145]
Identifiant IRD
fdi:010083145
Contact