Viral release from hiv‐i‐induced syncytia of cd4⁺ c8166 cells

Abstract

Infection of the permissive C8166 CD4+ lymphoid cell line with human immunodeficiency virus (HIV)-I rapidly leads to syncytium formation. Ultrastructural features of medium-sized (40 to 60 microns) syncytia and larger syncytia are presented, with emphasis upon HIV-I release from the syncytial surface and into intrasyncytial vacuoles. Although surface release of HIV-I is shown to diminish with increasing syncytial size, it does not totally stop. Massive HIV-I release and entrapment within intrasyncytial vacuoles is clearly apparent within the "foamy" multivacuolated zones within medium and large syncytia. Numerous multicored aberrant viruses are routinely detected within the intrasyncytial vacuoles, and double-budding events likewise are readily detectable at the vacuolar membranes, but less so at the syncytial surface. It is suggested that this observation may be a reflection of the more restricted availability of vacuolar membrane area for excessive viral budding as compared with that at the syncytial surface.

The ultrastructure of multinucleate giant cells

“…The second situation appears to be of particular importance in the case of herpes-and retroviral-induced cell fusion, where viral integration, replication and expression of viral proteins at the cell surface (Desportes et al, 1989) is required to induce MNGC formation (Kalgemaraman et al, 1990). In this situation viral inactivation by UV or gamma irradiation (Chaterjee and Hunter, 1980;Kitchen et al, 1989) prevents the fusion event, as assessed by the in vitro cellular syncytium-formation assay (e.g. Nagy et al, 1983).…”

“…Electron microscopical studies on the HIV-1 infection of suspension cultures of the permissive human C8166 HTLV-I transformed lymphoblastoid cell line have been performed by Harris et al (1989). From approximately two days post infection of the cell culture, viral-producing cells can be detected.…”

“…The somewhat limited data presented above serves to indicate that the HIV-1 infected C8166 lymphoblastid suspension culture system expresses a complex dynamic situation within which cellular events relating to: (1) viral integration, replication and release, (2) cell fusion, (3) MNGC formation and (4) MNGC ageing and death can be investigated at the ultrastructural level. The survey presented represents only a small fraction of the available data, some of which has already been published elsewhere (Harris et al, 1989: Harris, 1990).…”

“…A hypothesis for T-cell dysfunction and depletion within the AIDS patient has recently been advanced by Ameisen and Capron (1991), within the framework of "programmed cell death" or apoptosis (Laurent-Crawford et al, 1991). On the other hand, it is certainly not beyond the bounds of possibility that the slow incorporation of activated viral-producing CD4 + lymphocytes, available from the pool of latently infected cells (McElrath et al, 1991;Zack et al, 1991), into binucleate or trinucleate cells following fusion with uninfected lymphocytes could account for the CD4 + (helper) T-lymphocyte depletion (Fauci, 1988;Haseltine, 1990Haseltine, , 1991Harris et al, 1989). This would be very difficult to detect histologically, for the reasons previously advanced (Section I), except when larger MNGCs are formed.…”

“…MNGCs have been detected in the lymph nodes (Beneviste et al, 1988), lung, spleen and brain of AIDS patients and primates infected with SIV, but not in buffy coat lymphocytes. It is reasonable to expect that any bi-or tri-nucleate cells present in the circulation would be selectively removed by passage through the spleen and thereby go undetected in samples taken from the peripheral circulation (Harris et al, 1989;Haseltine, 1990). Undoubtedly, because of the very low numbers of activated viral-producing cells during the earlier stages of AIDS/ARC, there will be a vast excess (some 1:500 to 1:50,000) of non-infected or unactivated latently infected circulatory and tissue CD4 + T-lymphocytes available for fusion.…”