title: Tat mutations in an African cohort that do not prevent transactivation but change its immunogenic properties.
abstract: Humoral responses against extra-cellular HIV-1 Tat may be beneficial as Tat has been implicated in the viral pathogenesis associated with HIV-1 disease progression. We determined the levels of anti-Tat IgG in sera of HIV-1 seropositive individuals from the Rural Clinical Cohort in Uganda using nine different Tat proteins representative of the major subtypes presently accounting for 97% of infections worldwide. We observed the presence of anti-Tat IgG able to react against the various subtypes tested, although none cross-reacted against all nine variants. We show that 46.25% of seropositive patients were able to recognise at least one Tat variant with 1:1000 sera dilution. We also show that the C terminus of Tat is the most variable region and an important epitope that might explain the limitation of cross-recognition of Tat antibodies regarding Tat variants. This study shows in seropositive patients that Tat can tolerate mutations without modification of its primary function but with changes in its immunogenic properties. These findings should be considered when designing Tat-based HIV-1 vaccines.
authors.affiliation: CNRS Formation de Recherche en Evolution 2737, Faculté de Pharmacie, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Campbell
authors.forename: David
authors.initials: D
authors.lastname: Senkaali
authors.forename: Jennifer
authors.initials: J
authors.lastname: Watkins
authors.forename: Didier
authors.initials: D
authors.lastname: Esquieu
authors.forename: Sandrine
authors.initials: S
authors.lastname: Opi
authors.forename: David L
authors.initials: DL
authors.lastname: Yirrell
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Erwann P
authors.initials: EP
authors.lastname: Loret
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D015331:Cohort Studies; D003429:Cross Reactions; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011817:Rabbits; D012424:Rural Population; D015533:Transcriptional Activation; D014454:Uganda; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: D015483:HIV Antibodies; D007074:Immunoglobulin G; D054322:tat Gene Products, Human Immunodeficiency Virus