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A pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency
P Ten Haaft1, B Verstrepen, K Uberla
1Department of Virology, Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands.
Abstract:
To determine if a specific pathogenic threshold of plasma viral RNA could be defined irrespective of virus strain, RNA levels in the plasma of more than 50 infected rhesus macaques (Macaca mulatta) were measured. Animals were inoculated intravenously with either simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) strains of known pathogenic potential (SIV8980, SIVsmm-3, SIVmac32H/J5, SIVmac32H/1XC, reverse transcriptase-SHIV, SHIV89.6p) or with attenuated strains (SHIVW6.1D, SHIVsf13, SHIVhan-2, SIVmacDeltanef, SHIVsf33). In animals inoculated with nonpathogenic strains, shortly after the primary peak of viremia viral RNA levels declined and remained below 10(4) RNA equivalents/ml of plasma between 6 and 12 weeks postinoculation. Animals infected with documented pathogenic strains maintained viral RNA levels higher than 10(5) RNA equivalents/ml of plasma. In animals infected with strains with low virulence, a decline in plasma RNA levels was observed, but with notable individual variation. Our results demonstrate that the disease-causing potential was predicted and determined by a threshold plasma virus load which remained greater than 10(5) RNA equivalents/ml of plasma 6 to 12 weeks after inoculation. A threshold virus load value which remained below 10(4) RNA equivalents/ml of plasma was indicative of a nonpathogenic course of infection.
Insights
A specific plasma viral RNA threshold predicts simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) pathogenicity. Viral loads above 10^5 RNA equivalents/ml indicate a pathogenic course, while below 10^4 suggests nonpathogenicity.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Viral load is a key indicator of disease progression in lentiviral infections.
- Defining a universal pathogenic threshold for simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) is crucial for understanding disease dynamics.
Purpose of the Study:
- To establish a specific pathogenic threshold for plasma viral RNA, independent of the SIV or SHIV strain used.
- To correlate plasma viral RNA levels with the pathogenic potential of different SIV and SHIV strains in rhesus macaques.
Main Methods:
- Quantified plasma viral RNA levels in over 50 rhesus macaques (Macaca mulatta) infected with various pathogenic or attenuated SIV and SHIV strains.
- Monitored viral RNA levels between 6 and 12 weeks post-inoculation to assess disease course.
Main Results:
- Infection with nonpathogenic strains resulted in viral RNA levels below 10^4 RNA equivalents/ml plasma by 6-12 weeks post-inoculation.
- Infection with pathogenic strains consistently maintained viral RNA levels above 10^5 RNA equivalents/ml plasma.
- A clear threshold of plasma virus load ( > 10^5 RNA equivalents/ml) at 6-12 weeks post-inoculation predicted pathogenic outcomes.
Conclusions:
- Plasma viral RNA load serves as a reliable predictor of pathogenic potential for SIV and SHIV infections.
- A threshold of > 10^5 RNA equivalents/ml plasma at 6-12 weeks post-inoculation indicates a pathogenic infection, while < 10^4 indicates a nonpathogenic course.