CD4 and infection: HIV Nef is released and transported by EVs, which cause bystander CD4 + T cells to undergo cellular senescence or death.438 Nef may reduce the quantity of CD4 incorporated into T cell EVs and degradation within the lysosomal compartment, preventing virions from attaching to vesicular CD4 and increasing the amount of virus in circulation that is available to infect the cell.439,440 Transfer of EVs with viral receptors to uninfected cells deficient in these receptors is another method that can render cells more vulnerable to infection, allowing these cells to become infected.