In vitro macrophage tropism of pathogenic and nonpathogenic molecular clones of simian immunodeficiency virus (SIVmac)
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B Banapour1, M L Marthas, R J Munn
1Department of Medical Pathology, University of California, Davis 95616.
Abstract:
The significance of infection of mononuclear phagocytes by immunodeficiency lentiviruses of primates is not clearly established. To explore the relationship of macrophage tropism and pathogenesis, conditions to culture and infect monocyte-derived macrophages from rhesus macaques were established and the growth properties of two molecular proviral clones of simian immunodeficiency virus (SIVmac) were studied. Rhesus macrophages supported productive infection of the nonpathogenic SIVmac-1A11 clone; extensive cytopathology characterized by formation of multinucleated giant cells and release of particle-associated reverse transcriptase activity in culture supernatant were observed. In contrast, the pathogenic SIVmac-239 did not establish a productive infection of macrophages and no cytopathology was observed. Both SIVmac-1A11 and SIVmac-239 replicated and induced cytopathic effects in cultures of rhesus peripheral blood lymphocytes and the Cemx174 lymphoid cell line. These results, together with the previously published reports on the pathogenic potential of these two clones of SIVmac, suggest that macrophage tropism measured in vitro does not correlate with in vivo virulence.
Insights
Simian immunodeficiency virus (SIVmac) infection of rhesus macaque macrophages revealed that the nonpathogenic SIVmac-1A11 clone caused significant cytopathology, while the pathogenic SIVmac-239 clone did not productively infect macrophages. Macrophage tropism in vitro does not predict in vivo virulence.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- The role of mononuclear phagocyte infection by primate lentiviruses, such as simian immunodeficiency virus (SIVmac), in disease pathogenesis remains unclear.
- Understanding macrophage tropism is crucial for elucidating lentiviral disease mechanisms.
Purpose of the Study:
- To investigate the relationship between macrophage tropism and simian immunodeficiency virus (SIVmac) pathogenesis.
- To establish conditions for culturing and infecting rhesus macaque monocyte-derived macrophages and study the growth properties of SIVmac clones.
Main Methods:
- Culture and infection of monocyte-derived macrophages from rhesus macaques.
- Assessment of growth properties and cytopathology of two SIVmac molecular proviral clones (SIVmac-1A11 and SIVmac-239).
- Analysis of viral replication and cytopathic effects in rhesus peripheral blood lymphocytes and the Cemx174 lymphoid cell line.
Main Results:
- Rhesus macrophages supported productive infection by the nonpathogenic SIVmac-1A11 clone, leading to extensive cytopathology (multinucleated giant cells) and reverse transcriptase activity.
- The pathogenic SIVmac-239 clone did not establish a productive infection in macrophages, with no observed cytopathology.
- Both SIVmac-1A11 and SIVmac-239 replicated and induced cytopathic effects in rhesus peripheral blood lymphocytes and the Cemx174 lymphoid cell line.
Conclusions:
- In vitro macrophage tropism of SIVmac clones does not correlate with their in vivo virulence.
- These findings challenge the assumption that productive infection of macrophages is a key determinant of lentiviral pathogenesis in vivo.