Defective HIV-1 quasispecies in the form of multiply drug-resistant proviral DNAwithin cells can be rescued by superinfection with different subtype variants of HIV-1 and by HIV-2 and SIV

摘要

Objectives: HIV-1 generates swarms of similar, but genetically distinct, variants termed quasispecies and manyof these variants can be defective. Arelevant question is whether such defective species can contribute to viral pathogenesis. Indeed, we previously reported that a presumed recombination of defective proviral DNAwith other complementary defective proviral DNA or with wild-type viral DNA in the aftermath of superinfection could lead to the rescue of defective provirus and the production of replication-competent virus. We then wished to determine whether such rescue could be affected by viruses of different subtypes or even by other members of the retrovirus family. Methods: Here, we have used drug resistance mutations within the HIV genome as markers of potential recombination. Results: We show that a defective proviral DNA within cells can be rescued by the superinfection of MT2 cells by various subtypes of HIV-1, and by HIV-2 and simian immunodeficiency virus, but not by human T cell leukaemia virus type 1 or by human herpes virus-6. The drug-resistance phenotype of the rescued HIV was confirmed in a second round of infection. Conclusions: Defective proviral HIV-1 can be rescued by the infection by different variants of HIV-1 and by several other retroviruses as well.