1. Tat mutations in an African cohort that do not prevent transactivation but change its immunogenic properties.
- Author
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Campbell GR, Senkaali D, Watkins J, Esquieu D, Opi S, Yirrell DL, Kaleebu P, and Loret EP
- Subjects
- Amino Acid Sequence, Animals, Circular Dichroism, Cohort Studies, Cross Reactions, Disease Progression, HIV Infections immunology, HIV Infections physiopathology, HIV Infections virology, HIV-1 genetics, Humans, Immunoglobulin G blood, Models, Molecular, Molecular Sequence Data, Rabbits, Rural Population, Uganda, tat Gene Products, Human Immunodeficiency Virus chemistry, tat Gene Products, Human Immunodeficiency Virus metabolism, HIV Antibodies blood, HIV-1 immunology, Mutation, Transcriptional Activation, tat Gene Products, Human Immunodeficiency Virus genetics, tat Gene Products, Human Immunodeficiency Virus immunology
- 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.
- Published
- 2007
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