Independent evolution of hypervariable regions of HIV-1 gp120: V4 as a swarm of N-Linked glycosylation variants.
In this study we have characterized intra-patient length polymorphism in V4 by cloning and sequencing a C2-C4 fragment from HIV plasma RNA in patients at different stages of HIV disease. Clonal analysis of clade B, G, and CRF02 isolates during early infection shows extensive intra-patient V4 variability, due to the presence of indel-associated polymorphism. Indels, coupled to amino acid substitution events, affect the number and distribution of potential N-glycosylation sites, resulting in the coexistence, within the same patient, of V4 subsets, each characterized by different sizes, amino acid sequences, and potential N-glycosylation patterns. In contrast, V3 appears to be relatively homogeneous, with similar V3 associated to significantly different V4 within the same clinical specimen. Based on these data, we propose that during early chronic infection V4 is present as a highly divergent quasispecies, enabling the virus to adopt different conformational structures according to immune constrains and other selective pressures.
Castro
Erika
E
Laboratory of AIDS Immunopathogenesis, CHUV, Lausanne, Switzerland.
Bélair
Manon
M
Rizzardi
Gian Paolo
GP
Bart
Pierre A
PA
Pantaleo
Giuseppe
G
Graziosi
Cecilia
C
D000208:Acute Disease; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002908:Chronic Disease; D019143:Evolution, Molecular; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D011110:Polymorphism, Genetic
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; C514793:gp120 protein, Human immunodeficiency virus 1