Virus isolates during acute and chronic human immunodeficiency virus type 1 infection show distinct patterns of sensitivity to entry inhibitors.
We studied the effect of entry inhibitors on 58 virus isolates derived during acute and chronic infection to validate these inhibitors in vitro and to probe whether viruses at early and chronic disease stages exhibit general differences in the interaction with entry receptors. We included members of all types of inhibitors currently identified: (i) agents that block gp120 binding to CD4 (CD4-IgG2 and monoclonal antibody [MAb] IgG1b12), (ii) compounds that block the interaction with CCR5 (the chemokine RANTES/CCL5, the small-molecule inhibitor AD101, and the anti-CCR5 antibody PRO 140), (iii) the fusion inhibitor enfuvirtide (T-20), and (iv) neutralizing antibodies directed against gp120 (MAb 2G12) and gp41 (MAbs 2F5 and 4E10). No differences between viruses from acute and chronic infections in the susceptibility to inhibitors targeting the CD4 binding site, CCR5, or fusion or to MAb 2G12 were apparent, rendering treatment with entry inhibitors feasible across disease stages. The notable exceptions were antibodies 2F5 and 4E10, which were more potent in inhibiting viruses from acute infection (P = 0.0088 and 0.0005, respectively), although epitopes of these MAbs were equally well preserved in both groups. Activities of these MAbs correlated significantly with each other, suggesting that common features of the viral envelope modulate their potencies.
Rusert
Peter
P
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.
Kuster
Herbert
H
Joos
Beda
B
Misselwitz
Benjamin
B
Gujer
Cornelia
C
Leemann
Christine
C
Fischer
Marek
M
Stiegler
Gabriela
G
Katinger
Hermann
H
Olson
William C
WC
Weber
Rainer
R
Aceto
Leonardo
L
Günthard
Huldrych F
HF
Trkola
Alexandra
A
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000208:Acute Disease; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D002908:Chronic Disease; D000077560:Enfuvirtide; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D012044:Regression Analysis
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide