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Human immunodeficiency virus-1 tat- and tat/nef-defective genomes containing HIV-regulated diphtheria toxin A chain gene inhibit HIV replication.
Croat Med J. 2002 Oct; 43(5):591-7.CM

Abstract

AIM

To assess the ability of human immunodeficiency virus-1 (HIV-1) tat- and tat/nef-defective genomes containing diphtheria toxin A chain gene (DTA) to inhibit replication of HIV in human cells.

METHODS

Plasmids were constructed to contain the HIV-1 genome disabled by tat and tat/nef deletions, and sequences coding for the A subunit of diphtheria toxin gene were inserted into one of these deletions. An infectious clone of HIV-1 (pBRU-3) was cotransfected into HeLa-CD4 cells, together with plasmids carrying the modified DTA-containing genomes. Cell culture supernatants were collected and titrated for the virus by multinuclear activation of beta-galactosidase (MAGI) assay.

RESULTS

Each of the DTA-containing plasmids suppressed HIV production by no less than 96%, whereas the defective non-DTA containing plasmids did not interfere with the virus growth. Plasmids containing wild-type DTA inhibited HIV replication slightly more than its moderately attenuated mutant form, probably by limiting the synthesis of viral proteins. These modified DTA-containing HIV constructs gave no evidence of virus growth in HIV susceptible cells that supported the multiplication of the parent plasmid. None of the modified DTA-containing plasmids was toxic to cells cotransfected with a selectable marker, as shown by the ability of cotransfectants to multiply and form colonies at rates identical to controls exposed to non-specific DNA. This suggested that DTA was probably not expressed in the absence of activating wild-type HIV plasmid.

CONCLUSION

HIV-regulated DTA in the background of a HIV replication and expression of defective provirus may be taken into consideration as a therapy approach to the treatment of HIV infection, based on its selective and specific toxicity only to HIV infected CD4-positive cells.

Authors+Show Affiliations

Department of Molecular Genetics, Ruder Bosković Institute, Bijenicka c. 54, 10000 Zagreb, Croatia. brdar@rudjer.irb.hrNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12402403

Citation

Brdar, Branko, et al. "Human Immunodeficiency Virus-1 Tat- and Tat/nef-defective Genomes Containing HIV-regulated Diphtheria Toxin a Chain Gene Inhibit HIV Replication." Croatian Medical Journal, vol. 43, no. 5, 2002, pp. 591-7.
Brdar B, Matulić M, Rubelj I, et al. Human immunodeficiency virus-1 tat- and tat/nef-defective genomes containing HIV-regulated diphtheria toxin A chain gene inhibit HIV replication. Croat Med J. 2002;43(5):591-7.
Brdar, B., Matulić, M., Rubelj, I., Ivanković, M., & Reich, E. (2002). Human immunodeficiency virus-1 tat- and tat/nef-defective genomes containing HIV-regulated diphtheria toxin A chain gene inhibit HIV replication. Croatian Medical Journal, 43(5), 591-7.
Brdar B, et al. Human Immunodeficiency Virus-1 Tat- and Tat/nef-defective Genomes Containing HIV-regulated Diphtheria Toxin a Chain Gene Inhibit HIV Replication. Croat Med J. 2002;43(5):591-7. PubMed PMID: 12402403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human immunodeficiency virus-1 tat- and tat/nef-defective genomes containing HIV-regulated diphtheria toxin A chain gene inhibit HIV replication. AU - Brdar,Branko, AU - Matulić,Maja, AU - Rubelj,Ivica, AU - Ivanković,Milena, AU - Reich,Edward, PY - 2002/10/29/pubmed PY - 2002/12/27/medline PY - 2002/10/29/entrez SP - 591 EP - 7 JF - Croatian medical journal JO - Croat Med J VL - 43 IS - 5 N2 - AIM: To assess the ability of human immunodeficiency virus-1 (HIV-1) tat- and tat/nef-defective genomes containing diphtheria toxin A chain gene (DTA) to inhibit replication of HIV in human cells. METHODS: Plasmids were constructed to contain the HIV-1 genome disabled by tat and tat/nef deletions, and sequences coding for the A subunit of diphtheria toxin gene were inserted into one of these deletions. An infectious clone of HIV-1 (pBRU-3) was cotransfected into HeLa-CD4 cells, together with plasmids carrying the modified DTA-containing genomes. Cell culture supernatants were collected and titrated for the virus by multinuclear activation of beta-galactosidase (MAGI) assay. RESULTS: Each of the DTA-containing plasmids suppressed HIV production by no less than 96%, whereas the defective non-DTA containing plasmids did not interfere with the virus growth. Plasmids containing wild-type DTA inhibited HIV replication slightly more than its moderately attenuated mutant form, probably by limiting the synthesis of viral proteins. These modified DTA-containing HIV constructs gave no evidence of virus growth in HIV susceptible cells that supported the multiplication of the parent plasmid. None of the modified DTA-containing plasmids was toxic to cells cotransfected with a selectable marker, as shown by the ability of cotransfectants to multiply and form colonies at rates identical to controls exposed to non-specific DNA. This suggested that DTA was probably not expressed in the absence of activating wild-type HIV plasmid. CONCLUSION: HIV-regulated DTA in the background of a HIV replication and expression of defective provirus may be taken into consideration as a therapy approach to the treatment of HIV infection, based on its selective and specific toxicity only to HIV infected CD4-positive cells. SN - 0353-9504 UR - https://www.unboundmedicine.com/medline/citation/12402403/Human_immunodeficiency_virus_1_tat__and_tat/nef_defective_genomes_containing_HIV_regulated_diphtheria_toxin_A_chain_gene_inhibit_HIV_replication_ DB - PRIME DP - Unbound Medicine ER -