Homologous and nonhomologous retroviral recombinations are both involved in the transfer by infectious particles of defective avian leukosis virus-derived transcomplementing genomes

Abstract

We previously described avian leukosis virus-based packaging cell lines that produce stocks of retroviral vectors in which replication-competent viruses were not detectable. However, following infection of target cells with these retroviral stocks, we recently obtained colonies resulting from the transmission of recombinant genomes. Here, we have analyzed their genetic structure and shown that (i) each of them results from recombination between the packaging-and integration-defective transcomplementing genomes and the retroviral vector; (ii) recombination probably occurred during the reverse transcription step, involving strand switching of the reverse transcription growing point from the infectious retroviral vector to the transcomplementing RNA; and (iii) sequence identity and nonhomologous sequences were both used for the strand switching.

Persistent Production of an Integrase-Deleted HIV-1 Variant with No Resistance Mutation and Wild-Type Proviral DNA in a Treated Patient

“…Another possibility is recombination at the level of the TACA homology at the deletion junction, with the insertion of an A, as previously shown with other retroviruses. 32 Other cases of adherent-treated patients with a low but detectable viral load for a long period, and without a resistance mutation, were reported. 33 Such instances have not previously been associated with a defective virus, but it would be advisable to further explore these cases.…”

A Replication-Competent Retrovirus Arising from a Split-Function Packaging Cell Line Was Generated by Recombination Events between the Vector, One of the Packaging Constructs, and Endogenous Retroviral Sequences

“…Indeed, recombination between gag-pol and env had already occurred before transfection with the vector construct. Others have found that an avain leukosis virus-based split-function packaging line released replication-defective particles bearing portions of the packaging constructs (7,8). It may be expected that transfer of such helper sequences will increase the chance of further recombination events which could lead to replication competence.…”

“…Since even short stretches with partial homology, of 8 to 10 nucleotides, favor recombination (18), homologous regions between vector and transcomplementing sequences have been virtually eliminated in improved retroviral vector systems (5,20). Although this measure would be expected to reduce markedly the chances of recombination between these elements, such events may still occur in nonhomologous regions (8). Also, it is difficult to avoid a small region of homology between the two separate packaging constructs, since the 3Ј end of pol overlaps with the 5Ј end of env.…”

Identifikasi Virus Avian Leukosis Sub Grup J pada Peternakan Ayam Petelur Komersial di Kabupaten Tangerang Tahun 2015

“…(Hauptli et al, 1997;Smith et al, 1998;Payne and Venugopal, 2000;Venugopal et al, 1998) (Crittenden et al, 1987;Pang et al, 2010). Dampak lain yang perlu menjadi perhatian adalah kemungkinan terjadinya mutasi varian baru yang disebabkan karena rekombinasi diantara beberapa sub grup yang bersirkulasi di lingkungan (Bai et al 1995;Girod et al 1996).…”