Human immunodeficiency virus type 1 clade A and D neurotropism: molecular evolution, recombination, and coreceptor use.
Human immunodeficiency virus type 1 (HIV-1) non-B clade viral infections of the brain have not been studied to date. Among nine AIDS patients from Nairobi, Kenya, infected with HIV-1 A (N = 5) or D (N = 4) clade strains, brain-derived HIV-1 env sequences displayed greater evolutionary distance than B clade brain-derived viruses (P < 0.001). Similarly, molecular diversity between matched brain and spleen env clones was clade-dependent and concentrated in the hypervariable V4 region (P < 0.001), with phylogenetic clustering of sequences derived from the same organ. Brain-derived A and D clade sequences displayed significantly lower ratios of nonsynonymous/synonymous substitution rates (d(N)/d(S)) compared to matched spleen-derived clones and brain-derived B clade viruses. Interclade recombination events were infrequently observed among the present env sequences. A chimeric virus containing the C2V3 region from an A clade brain-derived sequence preferentially used CD4 and CCR5 for infection. These findings demonstrate that differences in molecular diversity in brain-derived sequences were dependent on the individual clade and domain within the env gene, but both B and non-B clade brain-derived viruses exhibit a preference for CCR5 as a coreceptor.
Zhang
K
K
Department of Clinical Neuroscience, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.
Hawken
M
M
Rana
F
F
Welte
F J
FJ
Gartner
S
S
Goldsmith
M A
MA
Power
C
C
D015526:AIDS Dementia Complex / Q000503:physiopathology / Q000821:virology*; D000328:Adult; D000595:Amino Acid Sequence; D001921:Brain / Q000821:virology*; D015704:CD4 Antigens / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000378:metabolism*; D011995:Recombination, Genetic; D013154:Spleen / Q000821:virology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5