Rhesus monkey macrophages infected with simian immunodeficiency virus cause rapid lysis of CD4-bearing lymphocytes.
Inoculation of simian immunodeficiency virus into cultures of primary rhesus monkey macrophages or CD4-bearing transformed T lymphocytes resulted in persistent infection, with minimal virus replication in the macrophages and extensive replication in the lymphocytes. However, uninfected T cells added to infected macrophages underwent rapid fusion and lysis and were almost completely eliminated without the production of virus particles. Lysis required direct contact between the T cells and the infected macrophages, which enabled binding between CD4 on the former and viral gp120 on the latter to occur. This process was blocked by soluble CD4 and dextran sulphate. Neutralizing antibodies in the serum of an infected macaque prevented cell fusion by preventing infection of the macrophages. However, these antibodies did not prevent fusion when added to previously infected macrophages. Infected macrophages were incorporated into the syncytia of lymphocytes and continued incorporation of new lymphocytes into the syncytia required infected macrophages to be metabolically active. One inference from these studies is that infected macrophages in vivo could help mediate the well known depletion of T4 cells in patients with AIDS.
McEntee
M F
MF
Johns Hopkins University School of Medicine, Division of Comparative Medicine, Baltimore, Maryland 21205.
Sharma
D P
DP
Zink
M C
MC
Adams
R J
RJ
Flexner
C
C
Clements
J E
JE
Narayan
O
O
D000818:Animals; D000914:Antibodies, Viral; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D002455:Cell Division; D002459:Cell Fusion; D003588:Cytopathogenic Effect, Viral; D016264:Dextran Sulfate / Q000494:pharmacology; D015726:Giant Cells / Q000166:cytology; D006801:Humans; D006822:Hybrid Cells; D007106:Immune Sera; D008253:Macaca mulatta; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D012995:Solubility; D014779:Virus Replication
D000914:Antibodies, Viral; D015704:CD4 Antigens; D007106:Immune Sera; D016264:Dextran Sulfate