title: Functional relevance of nonsynonymous mutations in the HIV-1 tat gene within an epidemiologically-linked transmission cohort.
abstract: Here we investigated the nature and functional consequences of mutations in the HIV-1 tat gene within an epidemiologically-linked AIDS transmission cohort consisting of a non-progressing donor (A) and two normal progressing recipients (B and C). Multiple nonsynonymous mutations in the tat first exon were observed across time in all individuals. Some mutations demonstrated striking host specificity despite the cohort being infected with a common virus. Phylogenetic segregation of the tat clones at the time of progression to AIDS was also observed especially in recipient C. Tat clones supporting high levels of transactivation were present at all time points in all individuals, although a number of clones defective for transactivation were observed for recipient C in later time points. Here we show that the tat quasispecies in a linked transmission cohort diversify and evolve independently between hosts following transmission. It supports the belief that quasispecies variation in HIV-1 is a mechanism for selection towards defining a fitter gene variant that is capable of resisting the human immune system.
authors.affiliation: Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. haran.sivakumaran@qimr.edu.au
authors.forename: Haran
authors.initials: H
authors.lastname: Sivakumaran
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.forename: Brenda
authors.initials: B
authors.lastname: Beckholdt
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
authors.forename: David
authors.initials: D
authors.lastname: Harrich
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission* / Q000821:virology*; D015331:Cohort Studies; D005091:Exons; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D065227:Transfusion Reaction
chemical_list: D015696:Gene Products, tat