Susceptibility of HIV-1 plasma virus to complement-mediated lysis. Evidence for a role in clearance of virus in vivo.
This study was undertaken to directly assess the susceptibility of HIV-1 plasma virus to C-mediated lysis. Plasma from HIV-infected individuals was collected and ultracentrifuged over 20% sucrose to isolate virions from plasma components including anticoagulants, which inhibit C activity. Treatment with C alone in the absence of exogenously added Ab caused lysis of virus from all patients (n = 18) (range 14 to 86%). This lysis occurred via the classical C pathway and was not due to cross-reactive Abs in the C source. Protein A bound a fraction of isolated plasma virus and this binding was blocked by purified human Ig suggesting that anti-HIV Abs bound to plasma virus could be responsible for inducing C activation. A portion of virus bound to CR2 on cells in the absence of exogenously added C indicating that virus activated C in vivo. C levels from six of six patients were determined to be sufficient to lead to lysis of virus in vivo. Since plasma virus appeared more sensitive to C than primary isolates, isolated virus was evaluated for the presence of C control proteins. While primary isolate virions contained CD46, CD55, and CD59, only CD59 was detected on plasma virus. The results of this study strongly suggest that C is activated by a portion of plasma virus in vivo due to the binding of Ab. The resultant opsonization plus subsequent lysis may be important routes of clearance and destruction of plasma virus in infected persons.
Sullivan
B L
BL
Department of Immunology/Microbiology, Rush University, Chicago, IL 60612, USA.
Knopoff
E J
EJ
Saifuddin
M
M
Takefman
D M
DM
Saarloos
M N
MN
Sha
B E
BE
Spear
G T
GT
D015703:Antigens, CD / Q000032:analysis; D018958:CD55 Antigens / Q000032:analysis; D018957:CD59 Antigens / Q000032:analysis; D002460:Cell Line; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007163:Immunosorbent Techniques; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D013205:Staphylococcal Protein A; D013601:T-Lymphocytes / Q000821:virology; D014766:Viremia / Q000276:immunology* / Q000821:virology; D014771:Virion / Q000737:chemistry
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D013205:Staphylococcal Protein A; D003165:Complement System Proteins