Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. Export

@article{citeulike:4839627, abstract = {Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4(+) T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12-20 mo, viruses exhibited concentrated mutations at 17-34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.}, author = {Salazar-Gonzalez, J. F. and Salazar, M. G. and Keele, B. F. and Learn, G. H. and Giorgi, E. E. and Li, H. and Decker, J. M. and Wang, S. and Baalwa, J. and Kraus, M. H. and Parrish, N. F. and Shaw, K. S. and Guffey, M. B. and Bar, K. J. and Davis, K. L. and Ochsenbauer-Jambor, C. and Kappes, J. C. and Saag, M. S. and Cohen, M. S. and Mulenga, J. and Derdeyn, C. A. and Allen, S. and Hunter, E. and Markowitz, M. and Hraber, P. and Perelson, A. S. and Bhattacharya, T. and Haynes, B. F. and Korber, B. T. and Hahn, B. H. and Shaw, G. M.}, citeulike-article-id = {4839627}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.20090378}, citeulike-linkout-1 = {http://jem.rupress.org/cgi/content/abstract/206/6/1273}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19487424}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19487424}, day = {8}, doi = {10.1084/jem.20090378}, issn = {1540-9538}, journal = {The Journal of experimental medicine}, keywords = {computation, infection}, month = {June}, number = {6}, pages = {1273--1289}, posted-at = {2009-06-29 11:03:53}, priority = {2}, title = {Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.}, url = {http://dx.doi.org/10.1084/jem.20090378}, volume = {206}, year = {2009} }

TY - JOUR ID - citeulike:4839627 L3 - citeulike-article-id:4839627 N2 - Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4(+) T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12-20 mo, viruses exhibited concentrated mutations at 17-34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses. IS - 6 JF - The Journal of experimental medicine SN - 1540-9538 EP - 1289 TI - Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. VL - 206 SP - 1273 KW - computation KW - infection AU - Salazar-Gonzalez, JF AU - Salazar, MG AU - Keele, BF AU - Learn, GH AU - Giorgi, EE AU - Li, H AU - Decker, JM AU - Wang, S AU - Baalwa, J AU - Kraus, MH AU - Parrish, NF AU - Shaw, KS AU - Guffey, MB AU - Bar, KJ AU - Davis, KL AU - Ochsenbauer-Jambor, C AU - Kappes, JC AU - Saag, MS AU - Cohen, MS AU - Mulenga, J AU - Derdeyn, CA AU - Allen, S AU - Hunter, E AU - Markowitz, M AU - Hraber, P AU - Perelson, AS AU - Bhattacharya, T AU - Haynes, BF AU - Korber, BT AU - Hahn, BH AU - Shaw, GM PY - 2009/06/08/ UR - http://dx.doi.org/10.1084/jem.20090378 ER -