Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection

Ma, Ge; Greenwell-Wild, Teresa; Lei, Kejian; Jin, Wenwen; Swisher, Jennifer; Hardegen, Neil; Wild, Carl T.; Wahl, Sharon M.

Whether the relative lack of abundance of annexin II on the perimeter of immature blood monocytes compared with mature macrophages influences their differential permissiveness to HIV-1 infection is of interest. A related, intriguing question is whether the viral tropism characteristic of T cell and macrophage targets bears any association with their divergent annexin II expression. Annexin II on mac-rophages may preferentially facilitate entry of virions expressing PS acquired during exit from prior macrophage hosts or from T cells undergoing apoptosis that only then express PS on their outer membrane leaflet (38, 39) , as compared with virions budded from PS-less viable T cells. R5 viruses mediate both mucosal and blood-borne transmission of HIV-1 infection, whereas the X4 (T tropic) viruses typically abound in the later stages of disease during clinical progression to AIDS (11, 40, 41) . Moreover, when infected T cells succumb to apoptosis, recognition of their newly exposed PS will promote clearance by annexin IIbearing macrophages with the potential for HIV-1 transfer (42) . It is conceivable that PS-annexin II interactions in the cytoplasmic vesicles and late endosomes of macrophages, where structural assembly of virions occurs (12, 43) and annexin II is found (28) , not only serve as a construction scaffolding, but also as a tether to retain virions intracellularly in a covert maneuver to avoid detection at the cell surface. Because the S100A10 component of the annexin II complex has been shown to facilitate arbovirus exocytosis (44), such a role in HIV-1 egress might also be considered. Annexin II/PS may also contribute to the host cell-derived cloak of the hypothetical Trojan exosomes that subversively deliver retroviral particles to nearby cells (45) , thus a co-conspirator with HIV-1 both going in and coming out.