Lectin-carbohydrate interactions and infectivity of human immunodeficiency virus type 1 (HIV-1).
The aim of this study was to determine whether mannosyl-specific lectins, especially Concanavalin A (ConA), may bridge HIV-1 env glycoproteins to cell membranes to increase virus binding to its targets, and to what extent this lectin-carbohydrate interaction can modify HIV-1 infectivity for monocytic compared with lymphoid cells. Monocytic U937 and lymphoid CEM cells, which both express surface mannose, were utilized. Whether first incubated with env glycoprotein or with the cells, lectins bound both to the cells and to radiolabeled recombinant gp160 (rgp160). Thus, they enhanced rgp160 adsorption to the cells in a methyl-alpha-mannose inhibitable manner. ConA did not appear to bind to the V1 domain of CD4 at the U937 cell surface since Leu3a binding was not blocked in the presence of ConA, nor was recombinant CD4 retained on a ConA-agarose affinity matrix. Moreover, enhanced rgp160 binding to the cells was CD4 independent, since it was not modified by preincubating the cells with Leu3a. Finally, ConA did not inhibit the binding of CD4-IgG3 chimeric molecules to virions immobilized on nitrocellulose membrane, which argues against the possibility that it interferes with the interaction of gp120 and CD4. However, both when incubated with the virus or with the cells and despite mediating enhanced binding of env glycoprotein, ConA neutralized HIV-1 infectivity for monocytic U937 as well as for lymphoid CEM cells. In this respect, ConA behaves like neutralizing antibodies which do not interfere with CD4 binding of gp120 but rather with some later event that leads to virus entry. These findings obtained with plant lectins may be of relevance in vivo, inasmuch as endogenous mannosyl-binding proteins, which are known to function as opsonins, have been reported to inhibit in vitro infection by HIV-1.
Gattegno
L
L
Laboratoire de Biologie Cellulaire, Faculté de Médecine Paris-Nord, Bobigny, France.
Ramdani
A
A
Jouault
T
T
Saffar
L
L
Gluckman
J C
JC
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000382:microbiology*; D002460:Cell Line; D015686:Gene Products, env / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism* / Q000502:physiology; D008214:Lymphocytes; D009000:Monocytes; D009500:Neutralization Tests; D011498:Protein Precursors / Q000378:metabolism; D011975:Receptors, Mitogen / Q000187:drug effects; D011991:Receptors, Virus / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D037102:Lectins; D011498:Protein Precursors; D011975:Receptors, Mitogen; D011991:Receptors, Virus; D011994:Recombinant Proteins