PT  - JOURNAL ARTICLE
AU  - Armita Nourmohammad
AU  - Jakub Otwinowski
AU  - Marta Łuksza
AU  - Thierry Mora
AU  - Aleksandra M. Walczak
TI  - Clonal competition in B-cell repertoires during chronic HIV-1 infection
AID  - 10.1101/271130
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 271130
4099  - http://biorxiv.org/content/early/2018/02/24/271130.short
4100  - http://biorxiv.org/content/early/2018/02/24/271130.full
AB  - During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host’s adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the modes of immune response are still unknown. Traditional population genetics methods fail to distinguish a chronic immune response from natural repertoire evolution in healthy individuals. Here, we infer the evolutionary modes of B-cell repertoire response and identify a complex dynamics where, instead of one winning clone, there is a constant production of new better mutants that compete with each other. A substantial fraction of mutations in pathogen-engaging CDRs of B-cell receptors are beneficial, in contrast to the many deleterious changes in structurally relevant framework regions. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix, challenging current vaccine design and therapy ideas.