Impaired immune evasion in HIV through intracellular delays and multiple infection of cells

Althaus, Christian; De Boer, Rob J (2012). Impaired immune evasion in HIV through intracellular delays and multiple infection of cells. Proceedings of the Royal Society. Series B - biological sciences, 279(1740), pp. 3003-10. London: Royal Society of London 10.1098/rspb.2012.0328

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Althaus, Christian

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0962-8452

Publisher:

Royal Society of London

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:36

Last Modified:

06 Mar 2019 13:43

Publisher DOI:

10.1098/rspb.2012.0328

PubMed ID:

22492063

Web of Science ID:

000306105900015

BORIS DOI:

10.7892/boris.14385

URI:

https://boris.unibe.ch/id/eprint/14385 (FactScience: 221352)

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