Analysis of HIV quasispecies suggests compartmentalization in the liver

Abstract

Liver disease is now a major cause of morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). An increasing body of evidence suggests that HIV infection is associated with exacerbated liver fibrosis and that HIV has the ability to infect several hepatic cell types. Despite the recognized existence of genetically distinct subpopulations of HIV in the central nervous system and genital tract, viral diversity and compartmentalization in the liver have not been explored extensively. Therefore, phylogenetic analysis was performed on full-length env and nef sequences for four patients. Distinct clustering of viral variants was observed for all patients in both areas of the genome. Statistical evidence of HIV compartmentalization in the liver was demonstrated in 85.4% of comparisons. Signature sequence analysis identified several liver-specific amino acids in all patients. Thus, the current study demonstrates statistically significant evidence for HIV compartmentalization in the liver. Additionally, these data suggest that the hepatic microenvironment harbors unique selective pressures that drive viral adaptation.

FIG. 1.

Intrapatient phylogenetic trees of (A) V3 loop variants from patient HIV_ams198, (B) gp120 variants from patient DY, and (C) gp120 variants from patient AZ. Shown in the lower left corner is a bar depicting the percent genetic distance for each tree. Compartmentalization is observed only in the liver and brain tissues. PBMC, peripheral blood mononuclear cells; CSF, cerebrospinal fluid. Only relevant bootstrap values greater than 700 out of 1,000 are shown. Sequence data for patient HIV_ams198 were originally reported in Van't Wout et al. Sequence data for patients AZ and DY were originally reported in Lamers et al.

FIG. 2.

Intrapatient phylogenetic trees of gp120 variants from patient AM. Shown in the lower left corner is a bar depicting the percent genetic distance for each tree. Only relevant bootstrap values greater than 700 out of 1,000 are shown. Sequence data were originally reported in Lamers et al.

FIG. 3.

Intrapatient phylogenetic trees of (A) nef variants from patient DY and (B) nef variants from patient AZ. Shown in the lower left corner is a bar depicting the percent genetic distance for each tree. Only relevant bootstrap values greater than 700 out of 1,000 are shown. Sequence data were originally reported in Lamers et al.

FIG. 4.

Intrapatient phylogenetic trees of nef variants from patient AM. Shown in the lower left corner is a bar depicting the percent genetic distance for each tree. Only relevant bootstrap values greater than 700 out of 1,000 are shown. Sequence data were originally reported in Lamers et al.