Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2010 Aug 12;6(8):e1000883. doi: 10.1371/journal.pcbi.1000883

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

PMC Copyright notice

(A) Diagram of the baseline model, which considers only a single sensitive viral strain. Two types of T cells are considered: gene-modified cells which are protected from infection (shown in red) and non-modified cells that are susceptible to it (shown in blue). The proliferation rate of both cell populations is determined by a saturating function, , which takes a Michaelis-Menten form. Therapy effects are conveyed via an infectivity inhibition factor () for gene-modified cells. (B) An example of a possible evolutionary path towards the emergence of a highly resistant strain. A genetic barrier corresponds to a set of three resistance-conferring sites (hashes), where any combination of these sites can be mutated (stars). At each integration step of the simulation, a strain may only accrue a single mutation in one of the non-mutated sites. The degree of resistance is determined by the number of mutations (), and is manifested as improved infection of P cells (i.e., higher infection rates due to an increase in ). Mutations are also associated with a loss in fitness that negatively affects the ability of these mutants to infect U cells, and that also depends on the number of mutations.

Inline graphic — (A) Diagram of the baseline model, which considers only a single sensitive viral strain. Two types of T cells are considered: gene-modified cells which are protected from infection (shown in red) and non-modified cells that are susceptible to it (shown in blue). The proliferation rate of both cell populations is determined by a saturating function, , which takes a Michaelis-Menten form. Therapy effects are conveyed via an infectivity inhibition factor () for gene-modified cells. (B) An example of a possible evolutionary path towards the emergence of a highly resistant strain. A genetic barrier corresponds to a set of three resistance-conferring sites (hashes), where any combination of these sites can be mutated (stars). At each integration step of the simulation, a strain may only accrue a single mutation in one of the non-mutated sites. The degree of resistance is determined by the number of mutations (), and is manifested as improved infection of P cells (i.e., higher infection rates due to an increase in ). Mutations are also associated with a loss in fitness that negatively affects the ability of these mutants to infect U cells, and that also depends on the number of mutations.