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HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load
1Medical Research Council Laboratories, Fajara, The Gambia, West Africa.
Insights
Cytotoxic T-lymphocyte (CTL) responses against HIV-2 proteins were observed in most infected individuals. Higher CTL activity correlated with lower HIV-2 proviral load, suggesting CTLs control viral replication.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Human Immunodeficiency Virus type 2 (HIV-2) infection is a significant global health concern.
- Understanding the host immune response, particularly cytotoxic T-lymphocyte (CTL) activity, is crucial for controlling HIV-2 replication.
Purpose of the Study:
- To characterize HIV-2-specific CTL activities in HIV-2-infected individuals.
- To investigate the relationship between CTL responses and HIV-2 proviral load.
Main Methods:
- Peripheral blood mononuclear cells were collected from HIV-2-seropositive and HIV-1/2 dually seropositive subjects.
- CTL responses were assessed using a 51Cr-release assay against cells expressing HIV-2 Gag, Pol, or Nef proteins.
- HIV-2 proviral load was quantified using a quantitative radiometric assay based on polymerase chain reaction (PCR).
Main Results:
- CTL responses against HIV-2 Gag and Pol proteins were detected in 90% and 70% of subjects, respectively.
- Responses against Nef protein were observed in 25% of subjects, with many recognizing multiple viral proteins.
- A strong inverse correlation was found between the level of HIV-2-specific CTL activity and HIV-2 proviral load.
Conclusions:
- HIV-2-specific CTL responses targeting multiple viral proteins are common in infected individuals.
- The observed inverse correlation supports the role of CTLs in controlling HIV-2 replication.
- These findings highlight the importance of cellular immunity in managing HIV-2 infection.
Objectives:
To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activities in HIV-2-infected individuals and to relate these to HIV-2 proviral load.
Methods:
Peripheral blood mononuclear cells were collected from 16 HIV-2-seropositive and four HIV-1/2 dually seropositive subjects. CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard 51Cr-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein. Proviral load was quantified by polymerase chain reaction (PCR) which used HIV-2 long terminal repeat primers and an external standard control made by an HIV-2CBL-22 chronically infected C8166 cell line. A biotinylated primer was used to capture the 35S dATP-incorporated secondary PCR product in a quantitative radiometric assay.
Results:
After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, respectively, whereas a CTL response was noted against Nef protein in five (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multiple HIV proteins were simultaneously recognized. The sum of specific lysis (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio, or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r = -0.625, P = 0.003 and r = -0.674, P = 0.001, respectively).
Conclusion:
HIV-2-specific CTL to multiple gene products was demonstrated in most HIV-2-infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis that CTL are important in the control of HIV-2 replication.