Related Experiment Videos
Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa
M P Cranage1, A M Whatmore, S A Sharpe
1Centre for Applied Microbiology and Research, Salisbury, Wiltshire, United Kingdom. martin.cranage@camr.org.uk
Abstract:
Good protection against systemic challenge in the SIVmac model of AIDS has been provided by prior infection with attenuated virus. To determine if such protection extends to intrarectal mucosal challenge two molecular clones, SIVmacC8 and SIVmacJ5, were used in this study. SIVmacC8 has an attenuated phenotype in vivo, due to a 12-bp deletion in the nef/ 3'-LTR, whereas SIVmacJ5 has a full size nef open reading frame and induces AIDS in infected macaques. The J5 molecular clone was shown to infect rhesus macaques following atraumatic intrarectal inoculation. The dynamics were similar to those following intravenous inoculation resulting in early, high, cell-associated viremia and seroconversion. Four macaques previously infected with the attenuated SIVmacC8 resisted superinfection with SIVmacJ5, following intrarectal inoculation. These animals also resisted intrarectal infection with an HIV/SIV chimeric virus (SHIV) composed of SIVmac239 expressing the HXBc2 env, tat, and rev genes, suggesting that immunity to the envelope proteins was unlikely to be involved in the superinfection resistance. Infection with the attenuated SIVmac generated cytotoxic T lymphocytes (CTL) detectable in the peripheral circulation, serum neutralizing antibodies, and SIV-binding antibodies in rectal fluids. SIVmacC8 proviral DNA was found in lymph nodes removed at necropsy but there was no evidence for local sequestration of challenge virus. SIV-specific CTL, were detected in gut-associated lymph nodes and may have a role in limiting superinfection following mucosal exposure.
Insights
Prior infection with attenuated simian immunodeficiency virus (SIV) protected macaques from intrarectal challenge. This immunity involved cytotoxic T lymphocytes (CTL) in gut-associated lymph nodes, not just envelope protein immunity.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Prior infection with attenuated simian immunodeficiency virus (SIV) confers protection against systemic challenge.
- The SIVmac model in macaques is used to study AIDS pathogenesis and potential interventions.
Purpose of the Study:
- To investigate if prior infection with attenuated SIVmacC8 protects against intrarectal mucosal challenge with a pathogenic SIVmacJ5 clone.
- To explore the immune mechanisms underlying protection against mucosal SIV challenge.
Main Methods:
- Used two SIVmac molecular clones: SIVmacC8 (attenuated) and SIVmacJ5 (pathogenic).
- Inoculated rhesus macaques intrarectally with SIVmacJ5 after prior infection with SIVmacC8.
- Assessed protection by monitoring for infection and measured immune responses, including cytotoxic T lymphocytes (CTL) and antibodies.
Main Results:
- Macaques previously infected with attenuated SIVmacC8 resisted intrarectal superinfection with pathogenic SIVmacJ5.
- Protection extended to challenge with a chimeric HIV/SIV virus (SHIV), suggesting envelope protein immunity was not the primary mechanism.
- SIV-specific CTL were detected in peripheral circulation and gut-associated lymph nodes, indicating a role in mucosal immunity.
Conclusions:
- Prior infection with attenuated SIVmac provides robust protection against intrarectal mucosal challenge.
- Cellular immunity, particularly CTLs in the gut-associated lymphoid tissue, plays a crucial role in preventing superinfection after mucosal exposure.
- These findings support the potential of attenuated virus vaccines for preventing SIV/HIV transmission.