Open AccessHuman Immunodeficiency Virus Type 1 Subtypes Have a Distinct Long Terminal Repeat That Determines the Replication Rate in a Host-Cell-Specific Manner
Author(s) -
Tim van Opijnen,
Rienk E. Jeeninga,
Maarten C. Boerlijst,
Georgios Pollakis,
Veera Zetterberg,
Mika Salminen,
Ben Berkhout
Publication year - 2004
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.78.7.3675-3683.2004
Subject(s) - biology , viral replication , long terminal repeat , genetics , clone (java method) , conserved sequence , promoter , hiv long terminal repeat , virology , virus , gene , genome , gene expression , peptide sequence
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.