Role of the V2, V3, and CD4-binding domains of GP120 in curdlan sulfate neutralization sensitivity of HIV-1 during infection of T lymphocytes.
A sulfated polysaccharide, curdlan sulfate (CRDS) with 1,3-beta-D-glucan as a main chain, inhibits HIV-1 infection of human peripheral blood lymphocytes (PBLs) by binding to the V3 region of gp 120. We previously showed that T cell (T)-tropic HIV-1 isolates are over 10-fold more sensitive to neutralization by CRDS than macrophage (MT)-tropic viruses, which possesses a relatively less charged amino acid composition in the V3 sequence. To analyze the interaction of CRDS with V3 and its association with neutralization sensitivity of HIV-1 isolates, we examined the effect of CRDS on the binding of neutralizing antibodies to monomeric and oligomeric gp 120 mutants of T- and MT-tropic HIV-1 clones in which the V3 loop was either deleted or substituted by V3 of another isolate. Our results showed that the presence and the amino acid composition of the V3 loop appears to determine the extent of interaction of CRDS with the V2 and CD4-binding regions on native gp 120 monomers; however, the positive charge of V3 has less effect on this interaction on oligomeric gp 120. Furthermore, our results established that only the CRDS-induced masking of V3 on oligomeric gp120 appears to be associated with the anti-HIV-1 activity of CRDS in vitro. Our findings underline the usefulness of CRDS for understanding the structural constraints on gp 120 that drive the transition from MT- to T-tropic isolates in vivo and enable the virus to use multiple fusion cofactors.
Jagodzinski
P P
PP
Department of Microbiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Wustner
J
J
Kmieciak
D
D
Wasik
T J
TJ
Fertala
A
A
Sieron
A L
AL
Takahashi
M
M
Tsuji
T
T
Mimura
T
T
Fung
M S
MS
Gorny
M K
MK
Kloczewiak
M
M
Kaneko
Y
Y
Kozbor
D
D
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D005936:Glucans / Q000494:pharmacology*; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D017384:Sequence Deletion; D013045:Species Specificity; D013601:T-Lymphocytes / Q000821:virology*; D047071:beta-Glucans
D000998:Antiviral Agents; D015704:CD4 Antigens; D005936:Glucans; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D047071:beta-Glucans; C063130:curdlan sulfate