Virus threshold determines disease in SIVsmmPBj14-infected macaques.
Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial 10-fold doses of SIVsmmPBj14 clone bcl.3 spanning 10(-2) through 10(4)TCID50. The results revealed a strikingly narrow difference between minimum infectious and fatal disease-inducing doses and a close association between enteric lymphoid tissue virus burden and disease. All animals infected with as much as 10(4) TCID50 through as little as 100 TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection. Animals receiving 10(-1) TCID50 became infected (PCR+) but did not develop clinical disease. Animals receiving 10(-2) TCID50 did not become infected. The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total survival time increased slightly as virus input decreased from 10(4) to 10 degrees TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tissue (GALT), and lymph nodes and greatest lesion severity were attained at intermediate levels of virus input (10(1) to 10(2) TCID50), probably owing to optimal time for virus amplification in target tissues. The present study reinforces others on the PBj14 system, suggesting that once a threshold level of virus replication is attained in intestinal lymphoid tissues, the cascade of events precipitating the lethal PBj14 syndrome is triggered irreversibly.
O'Neil
S P
SP
Department of Pathology, Colorado State University, Fort Collins 80523, USA.
Mossman
S P
SP
Maul
D H
DH
Hoover
E A
EA
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000821:virology; D008254:Macaca nemestrina / Q000821:virology*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification; D012191:Retroviridae Proteins / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000472:pathogenicity*; D019562:Viral Load; D014764:Viral Proteins / Q000302:isolation & purification
D000914:Antibodies, Viral; D012191:Retroviridae Proteins; D014764:Viral Proteins; C040520:avian retrovirus proteins