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

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dc.contributor.authorNgandu, Nobubeloen_ZA
dc.contributor.authorSeoighe, Cathalen_ZA
dc.contributor.authorScheffler, Konraden_ZA
dc.date.accessioned2015-10-30T09:30:48Z
dc.date.available2015-10-30T09:30:48Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: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.identifier.apacitationNgandu, N., Seoighe, C., & Scheffler, K. (2009). Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission. <i>Virology Journal</i>, http://hdl.handle.net/11427/14510en_ZA
dc.identifier.chicagocitationNgandu, Nobubelo, Cathal Seoighe, and Konrad Scheffler "Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission." <i>Virology Journal</i> (2009) http://hdl.handle.net/11427/14510en_ZA
dc.identifier.citationNgandu, 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.ris TY - Journal Article AU - Ngandu, Nobubelo AU - Seoighe, Cathal AU - Scheffler, Konrad AB - 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. DA - 2009 DB - OpenUCT DO - 10.1186/1743-422X-6-164 DP - University of Cape Town J1 - Virology Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission TI - Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission UR - http://hdl.handle.net/11427/14510 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14510
dc.identifier.urihttp://dx.doi.org/10.1186/1743-422X-6-164
dc.identifier.vancouvercitationNgandu N, Seoighe C, Scheffler K. Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission. Virology Journal. 2009; http://hdl.handle.net/11427/14510.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2009 Ngandu et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceVirology Journalen_ZA
dc.source.urihttp://www.virologyj.comen_ZA
dc.subject.otherAdaptation, Biologicalen_ZA
dc.subject.otherSequence Analysis, DNAen_ZA
dc.subject.otherSimian immunodeficiency virusen_ZA
dc.titleEvidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmissionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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