Human immunodeficiency virus type 1 subtypes have a distinct long terminal repeat that determines the replication rate in a host-cell-specific manner

被引:79
作者
van Opijnen, T
Jeeninga, RE
Boerlijst, MC
Pollakis, GP
Zetterberg, V
Salminen, M
Berkhout, B
机构
[1] Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Sect Populat Biol Inst Biodivers & Ecosyst Dynam, NL-1098 SM Amsterdam, Netherlands
[3] Natl Publ Hlth Inst, Dept Infect Dis Epidemiol, FIN-00300 Helsinki, Finland
关键词
D O I
10.1128/JVI.78.7.3675-3683.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The long terminal repeat (LTR) transcriptional promoters of different human immunodeficiency virus (HIV) type 1 subtypes were inserted into the LAI molecular clone of subtype B. The viral genotypes represent seven subtypes (A, B, C, D, E, F, and G) and one circulating recombinant form (AG). We performed replication studies with this isogenic set of viruses across six cellular environments. This approach revealed strong cellular environment effects, but the method was not sensitive enough to detect small differences in the replication rate between the subtypes. By conducting pairwise competition experiments between the virus variants in six cellular environments, we could demonstrate significant differences in the replication rates of the subtypes and that LTR-determined viral fitness depends both on the host cell type and the activation state of the cell. In addition, we determined the degree of conservation of the transcription factor-binding sites (TFBS) in the different-subtype LTRs by analyzing sequences from the HIV sequence database. The sequence analyses revealed subtype-specific conservation of certain TFBS. The results indicate that one should consider the possibility of subtype-specific viral replication rates in vivo, which are strongly influenced by the host environment. We argue that the multidimensional host environment may have shaped the genetic structures of the subtype LTRs.
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收藏
页码:3675 / 3683
页数:9
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