Thus, HIV particles themselves do not directly cause pathogenesis and AIDS.

Conversely, it is the small

fraction of permissive cells that become productively infected and mediate cell-to-cell spread across
viral syn- apses culminating in the pyroptotic death on nonpermissive CD4 T cells. Thus, productively
infected cells, not free HIV particles, are the fundamental ‘‘killing units’’ of CD4 T cells in lymphoid
tissues. Productive (‘‘direct’’) and abor- tive (‘‘bystander’’) infections are therefore not independent
pathways of CD4 T cell depletion: they are linked in a single pathogenic cascade. Along with playing a
critical role in the virological synapse, the interaction of LFA-1 on T cells with ICAM-1 also mediates the
arrest and migration of leukocytes on surfaces of postcapillary venules at sites of infection or injury, as
well as the ability of these cells to crawl out of the blood stream be- tween high endothelial venules and
into lymph nodes (Girard et al., 2012). Importantly, IL-1b and other inflammatory signals increase the
expres- sion of adhesion molecules such as ICAM-1 on
endothelial cells