Superinfection of human immunodeficiency virus type 1 (HIV-1) to cell clone persistently infected with defective virus induces production of highly cytopathogenic HIV-1.
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.
Iwabu
Yukie
Y
Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan.
Goto
Toshiyuki
T
Tsuji
Shotaro
S
Warachit
Jiranan
J
Li
Gui-Mei
GM
Shoji
Sanae
S
Kameoka
Masanori
M
Ikuta
Kazuyoshi
K
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*
D012367:RNA, Viral