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A method to determine the duration of the eclipse phase for in vitro infection with a highly pathogenic SHIV strain.

Kakizoe Y, Nakaoka S, Beauchemin CA, Morita S, Mori H, Igarashi T, Aihara K, Miura T, Iwami S - Sci Rep (2015)

Bottom Line: If it is not, however, ignoring this delay affects the accuracy of the mathematical model, its parameter estimates, and predictions.Here, we introduce a new approach, consisting in a carefully designed experiment and simple analytical expressions, to determine the duration and distribution of the eclipse phase in vitro.We find that the eclipse phase of SHIV-KS661 lasts on average one day and is consistent with an Erlang distribution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Kyushu University, Fukuoka 812-8581, Japan.

ABSTRACT
The time elapsed between successful cell infection and the start of virus production is called the eclipse phase. Its duration is specific to each virus strain and, along with an effective virus production rate, plays a key role in infection kinetics. How the eclipse phase varies amongst cells infected with the same virus strain and therefore how best to mathematically represent its duration is not clear. Most mathematical models either neglect this phase or assume it is exponentially distributed, such that at least some if not all cells can produce virus immediately upon infection. Biologically, this is unrealistic (one must allow for the translation, transcription, export, etc. to take place), but could be appropriate if the duration of the eclipse phase is negligible on the time-scale of the infection. If it is not, however, ignoring this delay affects the accuracy of the mathematical model, its parameter estimates, and predictions. Here, we introduce a new approach, consisting in a carefully designed experiment and simple analytical expressions, to determine the duration and distribution of the eclipse phase in vitro. We find that the eclipse phase of SHIV-KS661 lasts on average one day and is consistent with an Erlang distribution.

No MeSH data available.


Related in: MedlinePlus

A schematic representation of the mathematical model. After a virion, , successfully enters and infects a susceptible target cell, , at infection rate, , the newly infected cell progresses through different stages of cell populations, , which are structured according to the time elapsed, , since virus entry. Each of these stages has a corresponding age-dependent hazard rate, , for the probability that the newly infected cell in the eclipse phase transitions to the infectious state (i.e., becomes infectious, ) and begins virus production. An infectious, virus-producing cell, , produces progeny virions at constant rate , and dies at rate . The virions are cleared at rate .
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f1: A schematic representation of the mathematical model. After a virion, , successfully enters and infects a susceptible target cell, , at infection rate, , the newly infected cell progresses through different stages of cell populations, , which are structured according to the time elapsed, , since virus entry. Each of these stages has a corresponding age-dependent hazard rate, , for the probability that the newly infected cell in the eclipse phase transitions to the infectious state (i.e., becomes infectious, ) and begins virus production. An infectious, virus-producing cell, , produces progeny virions at constant rate , and dies at rate . The virions are cleared at rate .

Mentions: To generalize the basic model and account for the duration of the eclipse phase, we introduce the age of infection, , corresponding to the time elapsed since the successful infection of a cell, i.e. since the start of the eclipse phase (Fig. 1). Following others, we will refer to cells which have the same age of infection, , as a cohort31. Let denote the cohort of cells which have reached age in the eclipse (non-infectious) phase at present time . The population of target and infectious (virus-producing) cells and the virus concentration, at time , continue to be represented by , , and , respectively. We assume that the rate of transition from the eclipse to the infectious phase for a cell that has already spent an age in the eclipse phase, is given by the hazard rate , whose definition32 is such that


A method to determine the duration of the eclipse phase for in vitro infection with a highly pathogenic SHIV strain.

Kakizoe Y, Nakaoka S, Beauchemin CA, Morita S, Mori H, Igarashi T, Aihara K, Miura T, Iwami S - Sci Rep (2015)

A schematic representation of the mathematical model. After a virion, , successfully enters and infects a susceptible target cell, , at infection rate, , the newly infected cell progresses through different stages of cell populations, , which are structured according to the time elapsed, , since virus entry. Each of these stages has a corresponding age-dependent hazard rate, , for the probability that the newly infected cell in the eclipse phase transitions to the infectious state (i.e., becomes infectious, ) and begins virus production. An infectious, virus-producing cell, , produces progeny virions at constant rate , and dies at rate . The virions are cleared at rate .
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440524&req=5

f1: A schematic representation of the mathematical model. After a virion, , successfully enters and infects a susceptible target cell, , at infection rate, , the newly infected cell progresses through different stages of cell populations, , which are structured according to the time elapsed, , since virus entry. Each of these stages has a corresponding age-dependent hazard rate, , for the probability that the newly infected cell in the eclipse phase transitions to the infectious state (i.e., becomes infectious, ) and begins virus production. An infectious, virus-producing cell, , produces progeny virions at constant rate , and dies at rate . The virions are cleared at rate .
Mentions: To generalize the basic model and account for the duration of the eclipse phase, we introduce the age of infection, , corresponding to the time elapsed since the successful infection of a cell, i.e. since the start of the eclipse phase (Fig. 1). Following others, we will refer to cells which have the same age of infection, , as a cohort31. Let denote the cohort of cells which have reached age in the eclipse (non-infectious) phase at present time . The population of target and infectious (virus-producing) cells and the virus concentration, at time , continue to be represented by , , and , respectively. We assume that the rate of transition from the eclipse to the infectious phase for a cell that has already spent an age in the eclipse phase, is given by the hazard rate , whose definition32 is such that

Bottom Line: If it is not, however, ignoring this delay affects the accuracy of the mathematical model, its parameter estimates, and predictions.Here, we introduce a new approach, consisting in a carefully designed experiment and simple analytical expressions, to determine the duration and distribution of the eclipse phase in vitro.We find that the eclipse phase of SHIV-KS661 lasts on average one day and is consistent with an Erlang distribution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Kyushu University, Fukuoka 812-8581, Japan.

ABSTRACT
The time elapsed between successful cell infection and the start of virus production is called the eclipse phase. Its duration is specific to each virus strain and, along with an effective virus production rate, plays a key role in infection kinetics. How the eclipse phase varies amongst cells infected with the same virus strain and therefore how best to mathematically represent its duration is not clear. Most mathematical models either neglect this phase or assume it is exponentially distributed, such that at least some if not all cells can produce virus immediately upon infection. Biologically, this is unrealistic (one must allow for the translation, transcription, export, etc. to take place), but could be appropriate if the duration of the eclipse phase is negligible on the time-scale of the infection. If it is not, however, ignoring this delay affects the accuracy of the mathematical model, its parameter estimates, and predictions. Here, we introduce a new approach, consisting in a carefully designed experiment and simple analytical expressions, to determine the duration and distribution of the eclipse phase in vitro. We find that the eclipse phase of SHIV-KS661 lasts on average one day and is consistent with an Erlang distribution.

No MeSH data available.


Related in: MedlinePlus