title: Impaired immune evasion in HIV through intracellular delays and multiple infection of cells.
abstract: With its high mutation rate, HIV is capable of escape from recognition, suppression and/or killing by CD8(+) cytotoxic T lymphocytes (CTLs). The rate at which escape variants replace each other can give insights into the selective pressure imposed by single CTL clones. We investigate the effects of specific characteristics of the HIV life cycle on the dynamics of immune escape. First, it has been found that cells in HIV-infected patients can carry multiple copies of proviruses. To investigate how this process affects the emergence of immune escape, we develop a mathematical model of HIV dynamics with multiple infections of cells. Increasing the frequency of multiple-infected cells delays the appearance of immune escape variants, slows down the rate at which they replace the wild-type variant and can even prevent escape variants from taking over the quasi-species. Second, we study the effect of the intracellular eclipse phase on the rate of escape and show that escape rates are expected to be slower than previously anticipated. In summary, slow escape rates do not necessarily imply inefficient CTL-mediated killing of HIV-infected cells, but are at least partly a result of the specific characteristics of the viral life cycle.
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, The Netherlands. christian.althaus@alumni.ethz.ch
authors.forename: Christian L
authors.initials: CL
authors.lastname: Althaus
authors.forename: Rob J
authors.initials: RJ
authors.lastname: De Boer
mesh_terms: D005075:Biological Evolution; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D008954:Models, Biological; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000821:virology*; D013997:Time Factors