Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission

 

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dc.contributor.author Ngandu, Nobubelo en_ZA
dc.contributor.author Seoighe, Cathal en_ZA
dc.contributor.author Scheffler, Konrad en_ZA
dc.date.accessioned 2015-10-30T09:30:48Z
dc.date.available 2015-10-30T09:30:48Z
dc.date.issued 2009 en_ZA
dc.identifier.citation Ngandu, N. K., Seoighe, C., & Scheffler, K. (2009). Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission. Virology journal, 6(164), 148. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/14510
dc.identifier.uri http://dx.doi.org/10.1186/1743-422X-6-164
dc.description.abstract BACKGROUND:The cytotoxic T-lymphocyte immune response is important in controlling HIV-1 replication in infected humans. In this immune pathway, viral peptides within infected cells are presented to T-lymphocytes by the polymorphic human leukocyte antigens (HLA). HLA alleles exert selective pressure on the peptide regions and immune escape mutations that occur at some of the targeted sites can enable the virus to adapt to the infected host. The pattern of ongoing immune escape and reversion associated with several human HLA alleles has been studied extensively. Such mutations revert upon transmission to a host without the HLA allele because the escape mutation incurs a fitness cost. However, to-date there has been little attempt to study permanent loss of CTL epitopes due to escape mutations without an effect on fitness. RESULTS: Here, we set out to determine the extent of adaptation of HIV-1 to three well-characterized HLA alleles during the initial exposure of the virus to the human cytotoxic immune responses following transmission from chimpanzee. We generated a chimpanzee consensus sequence to approximate the virus sequence that was initially transmitted to the human host and used a method based on peptide binding affinity to HLA crystal structures to predict peptides that were potentially targeted by the HLA alleles on this sequence. Next, we used codon-based phylogenetic models to quantify the average selective pressure that acted on these regions during the period immediately following the zoonosis event, corresponding to the branch of the phylogenetic tree leading to the common ancestor of all of the HIV-1 sequences. Evidence for adaptive evolution during this period was observed at regions recognised by HLA A*6801 and A*0201, both of which are common in African populations. No evidence of adaptive evolution was observed at sites targeted by HLA-B*2705, which is a rare allele in African populations. CONCLUSION: Our results suggest that the ancestral HIV-1 virus experienced a period of positive selective pressure due to immune responses associated with HLA alleles that were common in the infected human population. We propose that this resulted in permanent escape from immune responses targeting unconstrained regions of the virus. en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source Virology Journal en_ZA
dc.source.uri http://www.virologyj.com en_ZA
dc.subject.other Adaptation, Biological en_ZA
dc.subject.other Sequence Analysis, DNA en_ZA
dc.subject.other Simian immunodeficiency virus en_ZA
dc.title Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission en_ZA
dc.type Journal Article en_ZA
dc.rights.holder 2009 Ngandu et al; licensee BioMed Central Ltd. en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
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This is an Open Access article distributed under the terms of the Creative Commons Attribution License Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License