Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.
The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs) in the α2 helix (in C3) and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Alessandra
A
Cenci
Istituto Superiore di Sanità, Department of Technology and Health, Rome, Italy.
Giuseppe
G
D'Avenio
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Lara
L
Tavoschi
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Michele
M
Chiappi
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Simone
S
Becattini
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Maria Del Pilar
Mdel P
Narino
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Orietta
O
Picconi
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Daniela
D
Bernasconi
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Emanuele
E
Fanales-Belasio
Stellenbosch University, Division of Medical Virology, Stellenbosch, South Africa; Lancet Laboratories, Johannesburg, South Africa.
Eftyhia
E
Vardas
National Center Public Health Laboratory, Manzini, Swaziland.
Hosea
H
Sukati
Istituto Superiore di Sanità, Department of Infectious, Parasitic and Immunomediated Diseases, Rome, Italy.
Alessandra
A
Lo Presti
Istituto Superiore di Sanità, Department of Infectious, Parasitic and Immunomediated Diseases, Rome, Italy; University of Biomedical Campus, Rome, Italy.
Massimo
M
Ciccozzi
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Paolo
P
Monini
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Barbara
B
Ensoli
Istituto Superiore di Sanità, Department of Technology and Health, Rome, Italy.
Mauro
M
Grigioni
Istituto Superiore di Sanità, National AIDS Center, Rome, Italy.
Stefano
S
Buttò
D000222:Adaptation, Physiological / Q000502:physiology*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010802:Phylogeny
D015699:HIV Envelope Protein gp120