Early pathogenesis of disease caused by SIVsmmPBj14 molecular clone 1.9 in macaques.
We have studied the early pathogenesis of infection by molecular clone 1.9 of SIVsmmPBj14 in pig-tailed and cynomolgus macaques. Like the uncloned PBj14 parent, SIVsmmPBj14-1.9 consistently induced an acute clinical syndrome characterized by behavioral depression, fever, profuse diarrhea, dehydration, lymphadenopathy, splenomegaly, and mucocutaneous exanthema that began at 7 days postinfection (DPI). The acute clinical disease coincided with a marked cell-associated and cell-free viremia, during which SIV p27 was demonstrated in 4 to 68% of circulating mononuclear leukocytes between 4 and 17 DPI. Also characteristic were monocytosis and reductions in CD4+ and CD8+ T lymphocytes, as well as CD20+ B lymphocytes. The most profound depletion occurred in the CD44hi subset of CD4+ T cells. Unlike animals infected previously with uncloned or biologically cloned PBj14, however, all SIVsmmPBj14-1.9-infected macaques survived the acute-phase disease to progress to a chronic, largely asymptomatic phase of infection. Recovery from the acute-phase disease correlated with down modulation of virus replication and the appearance of antibodies to SIV Env and Gag proteins. Similar to the PBj14 parent, PBj14-1.9 targeted to intestine, spleen, bone marrow, lymph node, and cerebellum. Saliva contained substantial quantities of infectious virus and no viral antibodies during the early phase of infection. By contrast, saliva from chronically infected animals usually contained antibodies but no virus. This study extends previous work demonstrating that the acute clinical syndrome produced by SIVsmmPBj14 in pig-tailed macaques represents a unique model of lentiviral pathogenesis.
Israel
Z R
ZR
Department of Pathology, Colorado State University, Fort Collins 80523.
Dean
G A
GA
Maul
D H
DH
O'Neil
S P
SP
Dreitz
M J
MJ
Mullins
J I
JI
Fultz
P N
PN
Hoover
E A
EA
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001483:Base Sequence; D002474:Cell-Free System; D002490:Central Nervous System / Q000382:microbiology; D003001:Cloning, Molecular; D004279:DNA, Viral; D004064:Digestive System / Q000382:microbiology; D016131:Lymphocyte Subsets / Q000276:immunology; D008221:Lymphoid Tissue / Q000382:microbiology; D008252:Macaca fascicularis; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000276:immunology; D016133:Polymerase Chain Reaction; D012463:Saliva / Q000382:microbiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D014766:Viremia
D000914:Antibodies, Viral; D004279:DNA, Viral