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Replication-competent chimeric lenti-oncovirus with expanded host cell tropism

S Reiprich¹, B R Gundlach, B Fleckenstein

¹Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nurnberg, Germany.

Journal of Virology

|April 1, 1997

Summary

Xenotransplantation using baboon bone marrow in HIV-1 patients risks creating dangerous chimeric retroviruses. Hybrid simian-murine leukemia viruses showed expanded cell tropism, posing a significant risk for gene therapy and xenotransplantation safety.

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Area of Science:

Virology
Immunology
Genetics

Background:

Baboon bone marrow transplantation is being explored for treating HIV-1.
Baboon endogenous retroviruses (BER) raise concerns about chimeric virus emergence in xenotransplant recipients.

Purpose of the Study:

To investigate the replication competence of hybrid retroviruses created by combining simian immunodeficiency virus (SIV) and murine leukemia virus (MLV).
To assess the potential risks associated with chimeric viruses in xenotransplantation and gene therapy.

Main Methods:

Constructed a hybrid virus by replacing the env gene of SIV with that of an amphotropic MLV.
Propagated the hybrid virus in various human and non-human primate cell lines, including T-cell lines, peripheral blood mononuclear cells (PBMCs) from rhesus macaques, and CD4- B-cell lines.

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Main Results:

The SIV-MLV hybrid virus demonstrated successful propagation across multiple cell types, including human and primate cells.
The expanded cell tropism of the hybrid virus suggests a potential selective advantage over parental viruses.

Conclusions:

Emerging chimeric retroviruses pose a significant risk in xenotransplantation due to their potential for enhanced replication and broader tropism.
Caution is advised regarding the use of pseudotyped lentiviral vectors in human gene therapy due to similar risks.