CD4-negative cells bind human immunodeficiency virus type 1 and efficiently transfer virus to T cells

The ability of human immunodeficiency virus strain MN (HIVMN), a T-cell fin e-adapted strain of HIV, and X4 and R5 primary isolates to bind to various cell types was investigated. In general, HIVMN,, bound to cells at higher l evels than did the primary isolates. Virus bound to both CD4-positive (CD4( +)) and CD4-negative (CD4(-)) cells, including neutrophils, Raji cells, ton sil mononuclear cells, erythrocytes, platelets, and peripheral blood mononu clear cells (PBMC), although virus bound at significantly higher levels to PBMC. However, there was no difference in the amount of HIV that bound to C D4-enriched or CD4-depleted PBMC, Virus bound to CD4(-) cells was up to 17 times more infectious for T cells in cocultures than was the same amount of tell-free virus, Virus bound to nucleated cells was significantly more inf ectious than virus bound to erythrocytes or platelets, The enhanced infecti on of T cells by virus bound to CD4- tells was not due to stimulatory signa ls provided by CD4(-) cells or infection of CD4(-) cells. However, anti-CD1 8 antibody substantially reduced the enhanced virus replication in T cells, suggesting that virus that bound to the surface of CD4(-) cells is efficie ntly passed to CD4(+) T cells during cell-cell adhesion. These studies show that HIV binds at relatively high levels to CD4(-) cells and, once bound, is highly infectious for T cells, This suggests that virus binding to the s urface of CD4(-) cells is an important route for infection of T cells in vi vo.