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Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells.
Mol Ther. 2002 Nov; 6(5):645-52.MT

Abstract

Vectors based on the feline immunodeficiency virus (FIV) have been developed as an alternative to those based on another lentivirus, human immunodeficiency virus-1 (HIV-1), because of theoretical safety advantages. We compared the efficiency of gene transfer and expression in human and feline hematopoietic progenitors using second-generation HIV-1 and FIV-based vectors. Vector pairs were tested using either human cytomegalovirus or murine phospho-glycerate kinase (PGK) internal promoters and were pseudotyped with the vesicular stomatitis virus G protein (VSV-G). Vector proviral copy numbers were similar in human and feline hematopoietic primary cells and cell lines transduced by HIV-1 or FIV vectors, demonstrating that both vectors are able to transfer genes efficiently to these cell types. HIV-1 vectors were well expressed in human primary hematopoietic cells and cell lines. However, transgene expression from FIV vectors was almost undetectable in human hematopoietic cells. In contrast, the FIV vector was expressed well in primary hematopoietic feline cells and human non-hematopoietic cells, demonstrating that low transgene expression from the FIV vector is a phenomenon specific to human hematopoietic cells. Northern blot analysis demonstrated decreased vector transcript levels in human CEM cells transduced with FIV relative to cells transduced with HIV-1, despite high vector copy numbers. No evidence of vector transcript instability was seen in studies of transduced CEM cells treated with actinomycin D. We conclude that FIV vectors can transfer genes into human hematopoietic cells as effectively as HIV-1 vectors, but that unknown elements in the current FIV backbone inhibit expression from FIV vectors in human hematopoietic cells.

Authors+Show Affiliations

Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12409263

Citation

Price, Mary A., et al. "Expression From Second-generation Feline Immunodeficiency Virus Vectors Is Impaired in Human Hematopoietic Cells." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 6, no. 5, 2002, pp. 645-52.
Price MA, Case SS, Carbonaro DA, et al. Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells. Mol Ther. 2002;6(5):645-52.
Price, M. A., Case, S. S., Carbonaro, D. A., Yu, X. J., Petersen, D., Sabo, K. M., Curran, M. A., Engel, B. C., Margarian, H., Abkowitz, J. L., Nolan, G. P., Kohn, D. B., & Crooks, G. M. (2002). Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells. Molecular Therapy : the Journal of the American Society of Gene Therapy, 6(5), 645-52.
Price MA, et al. Expression From Second-generation Feline Immunodeficiency Virus Vectors Is Impaired in Human Hematopoietic Cells. Mol Ther. 2002;6(5):645-52. PubMed PMID: 12409263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells. AU - Price,Mary A, AU - Case,Scott S, AU - Carbonaro,Denise A, AU - Yu,Xiao-Jin, AU - Petersen,Denise, AU - Sabo,Kathleen M, AU - Curran,Michael A, AU - Engel,Barbara C, AU - Margarian,Hovanes, AU - Abkowitz,Janis L, AU - Nolan,Garry P, AU - Kohn,Donald B, AU - Crooks,Gay M, PY - 2002/11/1/pubmed PY - 2003/5/15/medline PY - 2002/11/1/entrez SP - 645 EP - 52 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol Ther VL - 6 IS - 5 N2 - Vectors based on the feline immunodeficiency virus (FIV) have been developed as an alternative to those based on another lentivirus, human immunodeficiency virus-1 (HIV-1), because of theoretical safety advantages. We compared the efficiency of gene transfer and expression in human and feline hematopoietic progenitors using second-generation HIV-1 and FIV-based vectors. Vector pairs were tested using either human cytomegalovirus or murine phospho-glycerate kinase (PGK) internal promoters and were pseudotyped with the vesicular stomatitis virus G protein (VSV-G). Vector proviral copy numbers were similar in human and feline hematopoietic primary cells and cell lines transduced by HIV-1 or FIV vectors, demonstrating that both vectors are able to transfer genes efficiently to these cell types. HIV-1 vectors were well expressed in human primary hematopoietic cells and cell lines. However, transgene expression from FIV vectors was almost undetectable in human hematopoietic cells. In contrast, the FIV vector was expressed well in primary hematopoietic feline cells and human non-hematopoietic cells, demonstrating that low transgene expression from the FIV vector is a phenomenon specific to human hematopoietic cells. Northern blot analysis demonstrated decreased vector transcript levels in human CEM cells transduced with FIV relative to cells transduced with HIV-1, despite high vector copy numbers. No evidence of vector transcript instability was seen in studies of transduced CEM cells treated with actinomycin D. We conclude that FIV vectors can transfer genes into human hematopoietic cells as effectively as HIV-1 vectors, but that unknown elements in the current FIV backbone inhibit expression from FIV vectors in human hematopoietic cells. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/12409263/Expression_from_second_generation_feline_immunodeficiency_virus_vectors_is_impaired_in_human_hematopoietic_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525001602907252 DB - PRIME DP - Unbound Medicine ER -