title: Superinfection of human immunodeficiency virus type 1 (HIV-1) to cell clone persistently infected with defective virus induces production of highly cytopathogenic HIV-1.
abstract: Superinfection with human immunodeficiency virus type 1 (HIV-1) in human subjects, defined as reinfection with a heterologous strain of HIV-1, has become a topic of great interest. To illustrate the significance of this occurrence, we performed HIV-1 superinfection of L-2 cells, which were isolated from MT-4 cells persistently infected with subtype B HIV-1 as a cell clone continuously producing defective HIV-1 particles. L-2 cells carrying provirus with a one-base insertion in the pol protease were superinfected with HIV-1 derived from primary isolates of subtype B or CRF01_AE. The kinetics of the superinfection in L-2 were very slow compared with those of primary infections in MT-4. Interestingly, L-2 shifted after superinfection to become a producer of highly cytopathogenic HIV-1. Molecular characterization revealed that superinfection occurred in only about 10% of the CRF01_AE-superinfected L-2, which carried provirus of both subtypes and produced viral particles containing genomic RNA of both subtypes. Surprisingly, such cytopathogenic HIV-1 showed predominantly the original subtype B phenotype. Thus, the mechanism of the production of cytopathic HIV-1 seemed to be mediated by trans complementation with pol products of superinfected CRF01_AE. These findings suggest the significance of long-lived infected cells as recipients for superinfection that could result in the generation of new HIV-1 variants with high virulence in patients who are off therapy or do not adhere to treatment, and may indicate the need for precautions against such superinfection.
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Iwabu
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Goto
authors.forename: Shotaro
authors.initials: S
authors.lastname: Tsuji
authors.forename: Jiranan
authors.initials: J
authors.lastname: Warachit
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Li
authors.forename: Sanae
authors.initials: S
authors.lastname: Shoji
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D003673:Defective Viruses / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D015751:Genes, pol; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D006801:Humans; D011533:Proviruses / Q000235:genetics / Q000472:pathogenicity; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*
chemical_list: D012367:RNA, Viral