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Rapid CD4(+) T-cell loss induced by human immunodeficiency virus type 1(NC) in uninfected and previously infected
F J Novembre1, J de Rosayro, S Nidtha
1Divisions of Microbiology and Immunology, Yerkes Regional Primate Research Center, Atlanta, Georgia 30322, USA. fnovembr@rmy.emory.du
Insights
This study shows a new human immunodeficiency virus type 1 (HIV-1) isolate from chimpanzee C499 is highly pathogenic. Inoculated chimpanzees rapidly lost CD4(+) T-cells, indicating severe disease progression.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Chimpanzees are key models for studying human immunodeficiency virus type 1 (HIV-1) pathogenesis.
- Understanding viral pathogenicity is crucial for developing effective interventions.
Purpose of the Study:
- To assess the pathogenicity of a novel HIV-1 isolate (HIV-1(NC)) derived from an AIDS-affected chimpanzee (C499).
- To compare the effects of HIV-1(NC) infection in a naive chimpanzee versus one with a chronic HIV-1 infection.
Main Methods:
- Two chimpanzees were inoculated with the HIV-1(NC) isolate.
- Peripheral CD4(+) T-cell counts, plasma HIV-1 RNA loads, and viral burden in lymph nodes were monitored.
- Viral genotyping was performed to identify the predominant strain post-infection.
Main Results:
- Chimpanzee C534, previously uninfected, showed rapid CD4(+) T-cell depletion (<26 cells/microl) within 14 weeks, with high plasma viral loads.
- Chimpanzee C459, chronically infected with HIV-1(LAV), experienced accelerated CD4(+) T-cell loss (<200 cells/microl) by 96 weeks post-HIV-1(NC) superinfection.
- HIV-1(NC) became the dominant viral genotype in C459, with significantly increased viral RNA in plasma and lymph nodes.
Conclusions:
- The HIV-1(NC) isolate is demonstrably more pathogenic in chimpanzees than previously described HIV-1 isolates.
- This isolate causes rapid and severe CD4(+) T-cell depletion, highlighting its potential virulence.
Abstract:
To investigate the pathogenicity of a virus originating in a chimpanzee with AIDS (C499), two chimpanzees were inoculated with a plasma-derived isolate termed human immunodeficiency virus type 1(NC) (HIV-1(NC)). A previously uninfected chimpanzee, C534, experienced rapid peripheral CD4(+) T-cell loss to fewer than 26 cells/microl by 14 weeks after infection. CD4(+) T-cell depletion was associated with high plasma HIV-1 loads but a low virus burden in the peripheral lymph node. The second chimpanzee, C459, infected 13 years previously with HIV-1(LAV), experienced a more protracted course of peripheral CD4(+) T-cell loss after HIV-1(NC) inoculation, resulting in fewer than 200 cells/microl by 96 weeks postinoculation. The quantities of viral RNA in the plasma and peripheral lymph node from C459 were below the lower limits of detection prior to inoculation with HIV-1(NC) but were significantly and persistently increased after superinfection, with HIV-1(NC) representing the predominant viral genotype. These results show that viruses derived from C499 are more pathogenic for chimpanzees than any other HIV-1 isolates described to date.
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