Designing a non-virulent HIV-1 strain: potential implications for vaccine and experimental research

Abstract

BACKGROUND: Culturing and working with wild type HIV virions may produce contamination and infection. The main objective of this study was to design a non-infective HIV-1 strain that can be used safely in research laboratories for various research topics on HIV life cycle and pathogenesis. METHODS: Non-infective HIV-1 strain (mzNL4-3) was designed by deleting a 2 Kb sequence of HIV-1 (NL4-3 strain) genome that codes reverse transcriptase (RT) and integrase (IN) enzymes. RESULTS: The deletion removed 95% of RT and 34% of IN peptide sequences and abolished the functions of these en- zymes totally. This deletion didn't produce any other alteration in HIV genome, not only in mRNA level but also in transcription or translation levels. We named this strain, mutated z NL4-3 (mzNL4-3). CONCLUSIONS: Our mutated HIV-1 virions can be produced by transforming any mammalian cell line with mzNL4-3 vector (pmzNL4-3) but these virions can not replicate in any competent target cell. Hence, it can be used for many of the HIV-1 researches in a level 2 lab. mzNL4-3 has also the major antigen markers of HIV-1, NY5 and LAV strains, which are the most common strains of HIV-1. Therefore, mzNL4-3 can also be considered as a choice for HIV-1 vac- cine investigation. Probably mzNL4-3 could be used for lab research and vaccine investigation.