2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 47(2013) N 2 p. 228-235;
M.R. Aghasadeghi1, R. Zabihollahi1*, S.M. Sadat1, M. Salehi2, S.H. Ashtiani3, R. Namazi2, N. Kashanizadeh4, K. Azadmanesh1

Production and Evaluation of Immunologic Characteristics of mzNL4-3, a Non-Infectious HIV-1 Clone with a Large Deletion in the Pol-Sequence

1Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran
2Department of pharmaceutical biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan , Iran
3Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
4Gynecology Department, Baghiata-allah Hospital, University of Baghiata-allah, Iran

Received - 2012-06-20; Accepted - 2012-08-09

Inactivation of integrase (IN) and reverse transcriptase (RT) can revoke the replication of HIV virions, and non-infectious HIV particles are desirable virus-like particle (VLP) vaccine candidates. Here, we produced inactive HIV-1 particles fit for vaccine and virological purposes by introducing a mutation into the pol sequence. Proviral DNA (pNL4-3) was cut at two points in the pol region using the BalI restriction enzyme and then religated. HEK 293T cells were transfected with the resultant plasmid (pmzNL4-3) to produce mutated virions. To confirm a production of VLPs and evaluate their biological activity the p24 load and syncytium formation (MT2 cells) were analyzed. The assay indicated that mzNL4-3 virions were assembled and contained functional envelope glycoproteins (ENV). In addition, mzNL4-3 virions were able to infect neither the MT2 nor HEK 293T cells. Furthermore, the immunogenicity of VLPs was investigated in a mouse model. According to the data on vaccinated mice, the titer of ENV-specific antibodies rose rapidly after a boosting injection. Moreover, lymphoid cells extracted from these mice proliferated after exposure to the antigen. The mzNL4-3 virus particles possessed immunogenic antigens of HIV and can effectively trigger humoral and CD4 immune responses. Non-infectious mzNL4-3 virions may also be used in biomedical experiments for improving the biological safety conditions. Moreover, the mzNL4-3 seems to be a promising candidate for further HIV-1 vaccine investigations.

human immunodeficiency virus, virus-like particles, reverse transcriptase, integrase, envelope glycoproteins, HIV-1 vaccine