Virus threshold determines disease in SIVsmmPBj14-infected macaques

Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in produc ing an acutely lethal enteropathic syndrome in pigtail macaques, To determi ne whether the nature of the PBj14 disease would be attenuated by decreasin g virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial Id-fold doses of SIVsmmPBj14 clon e bcl.3 spanning 10(-2) through 10(4) TCID50. The results revealed a striki ngly narrow difference between minimum infectious and fatal disease-inducin g doses and a close association between enteric lymphoid tissue virus burde n and disease, All animals infected with as much as 10(4) TCID50 through as little as 10(0) TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection, Animals receiving 10(-1) TCID50 became infecte d (PCR+) but did not develop clinical disease, Animals receiving 10(-2) TCI D50 did not become infected, The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total sur vival time increased slightly as virus input decreased from 10(4) to 10(0) TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tis sue (GALT), and lymph nodes and greatest lesion severity were attained at i ntermediate levels of virus input (10(1) to 10(2) TCID50), probably owing t o optimal time for virus amplification in target tissues, The present study reinforces others on the PBj14 system, suggesting that once a threshold le vel of virus replication is attained in intestinal lymphoid tissues, the ca scade of events precipitating the lethal PBj14 syndrome is triggered irreve rsibly.