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Early pathogenesis of disease caused by SIVsmmPBj14 molecular clone 1.9 in macaques
Z R Israel1, G A Dean, D H Maul
1Department of Pathology, Colorado State University, Fort Collins 80523.
Abstract:
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.
Insights
This study shows that a specific simian immunodeficiency virus (SIV) clone causes acute illness in macaques but allows survival to a chronic phase. This SIV model offers insights into lentiviral pathogenesis and disease progression.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a critical model for understanding human immunodeficiency virus (HIV) pathogenesis.
- Previous studies established SIVsmmPBj14 as a potent viral isolate inducing severe acute disease.
Purpose of the Study:
- To investigate the early pathogenesis of infection with molecular clone 1.9 of SIVsmmPBj14 in pig-tailed and cynomolgus macaques.
- To characterize the clinical, virological, and immunological changes during acute and chronic phases of infection.
Main Methods:
- Infection of macaques with SIVsmmPBj14 molecular clone 1.9.
- Monitoring of clinical signs, including behavioral changes, fever, diarrhea, and exanthema.
- Quantification of viremia (SIV p27), and analysis of lymphocyte populations (CD4+, CD8+, CD20+, CD44hi subset).
- Assessment of viral tropism in various tissues and detection of viral antibodies in saliva.
Main Results:
- SIVsmmPBj14-1.9 induced an acute clinical syndrome with fever, diarrhea, lymphadenopathy, and significant viremia.
- Marked depletion of CD4+ and CD8+ T lymphocytes, particularly the CD44hi subset, was observed.
- Unlike previous isolates, all macaques infected with clone 1.9 survived the acute phase and entered a chronic, asymptomatic infection.
- Virus replication decreased, and antibodies to SIV Env and Gag proteins appeared during recovery.
- SIVsmmPBj14-1.9 targeted multiple tissues, including the intestine, spleen, bone marrow, lymph node, and cerebellum.
- Infectious virus was present in saliva during early infection, while antibodies were detected in saliva during the chronic phase.
Conclusions:
- SIVsmmPBj14 molecular clone 1.9 induces a severe acute illness but allows for survival and progression to chronic infection in macaques.
- Recovery from acute disease is associated with reduced viral replication and development of humoral immunity.
- The study highlights the utility of this SIV clone as a unique model for lentiviral pathogenesis research, particularly for understanding disease progression and potential therapeutic interventions.