Genetic characterization of HIV type 1 long terminal repeat following vertical transmission.
Human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) sequences were characterized from six mother-infant pairs following vertical transmission. The LTR sequences exhibited a low degree of heterogeneity within mothers, within infants, and between epidemiologically linked mother-infant pairs. However, LTR sequences were more heterogeneous between epidemiologically unlinked individuals compared with linked mother-infant pairs. These data were further supported by low estimates of genetic diversity and clustering of each mother-infant pair's sequences into a separate subtree as well as the presence of common signature sequences between mother-infant pairs. The functional domains essential for LTR (promoter) function, including the promoter (TATAA), enhancers (three Sp-I and two NF-kappaB), the modulatory regions (two AP-I sites, two NFAT, one NF-IL6 site, one Ets-1, and one USF-1), and the TAR region were generally conserved among mother-infant pairs. Taken together, limited heterogeneity and conservation of functional domains in the LTR following vertical transmission support the notion that a functional LTR is critical in viral replication and pathogenesis in HIV-1-infected mothers and their infected infants.
Mehta
Roshni
R
Department of Immunobiology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
Ramakrishnan
Rajesh
R
Doktor
Katherine
K
Sundaravaradan
Vasudha
V
Ahmad
Nafees
N
D000328:Adult; D002675:Child, Preschool; D003001:Cloning, Molecular; D016000:Cluster Analysis; D017124:Conserved Sequence; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008969:Molecular Sequence Data; D009035:Mothers; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D020079:Terminal Repeat Sequences / Q000235:genetics*
D012367:RNA, Viral