Syncytium formation in cultured human lymphoid tissue: fusion of implanted HIV glycoprotein 120/41-expressing cells with native CD4+ cells.
While glycoprotein gp120/41 clearly causes HIV-infected cells to form syncytia in monolayers and in suspension, there is unfortunately scant knowledge on syncytium formation in tissues. We implanted gp120/41-expressing cells labeled with fluorescent particles inside blocks of human lymphoid tissue kept in long-term histoculture. Observed by confocal microscopy, together with immunohistochemical and morphological analysis of implanted cells, more than one-third of these gp120/41-expressing cells fused with native CD4+ cells of the host tissue, yielding small (three to five nuclei) syncytia. Such widespread fusion of gp120/41-expressing cells in tissue in vitro, together with the finding of increased virulence of syncytium-inducing isolates of HIV, support the hypothesis that syncytium formation within lymph tissue of HIV-infected individuals contributes to AIDS pathogenesis. This system and the methods developed may provide a way to study HIV-infected cells inside the very tissue whose destruction may prevent immune system repopulation.
Margolis
L B
LB
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glushakova
S
S
Baibakov
B
B
Zimmerberg
J
J
D018951:Antigens, CD20 / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D002459:Cell Fusion; D046508:Culture Techniques; D015726:Giant Cells / Q000166:cytology; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000502:physiology*; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D014066:Palatine Tonsil / Q000276:immunology / Q000821:virology*; D014616:Vaccinia virus / Q000235:genetics
D018951:Antigens, CD20; D017252:CD3 Complex; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41