A Pathogenic Threshold of Virus Load Defined in Simian Immunodeficiency Virus- or Simian-Human Immunodeficiency Virus-Infected Macaques

Abstract

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 (SIV 8980 , SIV smm-3 , SIV mac32H/J5 , SIV mac32H/1XC , reverse transcriptase-SHIV, SHIV 89.6p ) or with attenuated strains (SHIV W6.1D , SHIV sf13 , SHIV han-2 , SIV macΔnef , SHIV sf33 ). 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.