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Internalization of human immunodeficiency virus type I and other retroviruses by megakaryocytes and platelets
D Zucker-Franklin1, S Seremetis, Z Y Zheng
1Department of Medicine, New York University Medical Center, NY.
Abstract:
Direct infection of megakaryocytes and platelets by human immunodeficiency virus type I (HIV-I) or other retroviruses has not been demonstrated. To determine whether this could occur, murine bone marrow was co-cultivated with the amphotropic retrovirus-producing cell line PA317-N2, and freshly isolated normal human bone marrow and platelets were co-cultivated with HIV-infected H9 cells. In each case, ultrastructural analyses showed viruses within megakaryocytes and platelets. In murine specimens, the uptake of retrovirus was avid at all stages of differentiation. In human specimens, viral uptake was less frequent. These results suggest that direct infection of megakaryocytes could play a role in the pathophysiology of HIV-associated disease. In addition, these observations suggest that cells of the megakaryocyte lineage could serve as target cells in gene transfer experiments using retroviral-based vectors.
Insights
Human immunodeficiency virus type I (HIV-I) can directly infect megakaryocytes and platelets. This finding suggests a potential role for direct viral infection in HIV-associated disease and identifies megakaryocytes as potential targets for gene therapy.
Area of Science:
- Virology
- Hematology
- Cell Biology
Background:
- Direct infection of megakaryocytes and platelets by human immunodeficiency virus type I (HIV-I) or other retroviruses has not been previously demonstrated.
- Understanding the cellular targets of HIV-I is crucial for comprehending viral pathogenesis and developing effective therapies.
Purpose of the Study:
- To investigate the potential for direct infection of megakaryocytes and platelets by retroviruses, including HIV-I.
- To explore the implications of megakaryocyte and platelet susceptibility for HIV-I pathophysiology and gene transfer applications.
Main Methods:
- Co-cultivation of murine bone marrow with a retrovirus-producing cell line (PA317-N2).
- Co-cultivation of human bone marrow and platelets with HIV-infected H9 cells.
- Ultrastructural analysis to detect viral presence within megakaryocytes and platelets.
Main Results:
- Ultrastructural analyses confirmed the presence of viruses within megakaryocytes and platelets in both murine and human specimens.
- Murine megakaryocyte differentiation stages showed avid retroviral uptake.
- Human specimens exhibited less frequent, but detectable, viral uptake by megakaryocytes and platelets.
Conclusions:
- Direct infection of megakaryocytes by HIV-I is possible, suggesting a role in HIV-associated disease.
- Megakaryocyte lineage cells may serve as target cells for future retroviral-based gene transfer strategies.