Superinfection of HIV-2-preinfected macaques after rectal exposure to a primary isolate of SIVmac251
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L Wakrim1, R Le Grand, B Vaslin
1Service de Neurovirologie, Commissariat à l'Energie Atomique, DRM/DSV/SSA/CEA, Fontenay aux Roses, France.
Abstract:
To test the protection afforded by a weakly pathogenic HIV-2 isolate against the superinfection or development of SIV-induced disease, we intrarectally challenged six HIV-2-preinfected rhesus monkeys with a pathogenic isolate of SIVmac251. At the time of SIV challenge, none of these HIV-2-infected animals was positive for virus isolation, p27-Gag antigenemia, or HIV-2 provirus detection in PBMCs or peripheral lymph nodes. However, all monkeys exhibited anti-HIV-2 antibody titers ranging from 10(2) to 10(3). Neutralizing antibodies against the challenge SIV strain were also detected in two animals. After rectal exposure to SIVmac251, five of the six HIV-2-preinfected macaques were superinfected. SIVmac251 DNA sequences were detected repeatedly in the PBMCs of the five superinfected animals and the two controls, whereas no HIV-2 provirus was detected for 14 months postchallenge. The one monkey that resisted superinfection was negative for all SIV infection criteria. This monkey exhibited the highest anti-SIV ELISA and cross-neutralizing antibody titers on the day of SIV challenge. Preinfection with a weakly pathogenic HIV-2 ROD isolate protected one of six macaques from infection with the closely related pathogenic SIVmac251 isolate, but no protection from the progression of disease was evidenced in the other five.
Insights
Pre-infection with a weak HIV-2 strain partially protected macaques from SIV superinfection. One of six macaques resisted SIVmac251 infection, but others showed no disease progression protection.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Understanding cross-protection between simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) is crucial for vaccine development.
- Weakly pathogenic HIV-2 isolates may offer partial protection against superinfection with pathogenic SIV strains.
Purpose of the Study:
- To evaluate the protective effect of pre-existing HIV-2 infection against superinfection with a pathogenic SIVmac251 isolate in rhesus monkeys.
- To assess whether HIV-2 pre-infection influences the development of SIV-induced disease.
Main Methods:
- Six rhesus monkeys pre-infected with a weakly pathogenic HIV-2 ROD isolate were intrarectally challenged with pathogenic SIVmac251.
- Viral load, p27-Gag antigenemia, proviral DNA, and antibody titers (anti-HIV-2 and anti-SIV) were monitored pre- and post-challenge.
Main Results:
- Five out of six HIV-2-preinfected macaques became superinfected with SIVmac251, confirmed by SIVmac251 DNA detection in peripheral blood mononuclear cells (PBMCs).
- One macaque resisted SIV superinfection, exhibiting high anti-SIV ELISA and cross-neutralizing antibody titers.
- No significant difference in disease progression was observed between superinfected animals and controls, and HIV-2 provirus remained undetectable post-challenge.
Conclusions:
- Pre-infection with a weakly pathogenic HIV-2 isolate provided limited protection against SIVmac251 superinfection in one out of six macaques.
- HIV-2 pre-infection did not confer protection against the progression of SIV-induced disease in the majority of animals studied.