Complement Lysis Activity in Autologous Plasma Is Associated with Lower Viral Loads during the Acute Phase of HIV-1 Infection

Abstract

BackgroundTo explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus.Methods and FindingsSera from two groups of patients—25 with acute HIV-1 infection and 31 with chronic infection—were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env) proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies.ConclusionsCollectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

The good and evil of complement activation in HIV-1 infection

“…[14][15][16] Using a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of viral lysis by complement, Huber et al documented that complement (sera from HIV-1-infected patients)-mediated lysis activity against the HIV-1 primary virus was higher during chronic disease stages than during the acute phase. 17 They also found that plasma viral load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. 17 These effects were attributed to anti-envelope (Env) Abmediated complement-dependent lysis.…”

“…17 They also found that plasma viral load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. 17 These effects were attributed to anti-envelope (Env) Abmediated complement-dependent lysis. Together, these results indicate that Ab-mediated complement virion lysis develops rapidly and is effective early in the course of infection.…”

“…Together, these results indicate that Ab-mediated complement virion lysis develops rapidly and is effective early in the course of infection. 17 Moreover, the HIV-1 surface proteins gp41 and gp120 further enhance Ab-mediated complement activation by binding C1q or MBL, respectively. [18][19][20][21][22][23][24][25] Using serum from an uninfected C1q-or C3-deficient individual as a source of complement does not mediate any anti-HIV-1 activity, which indicates that the classical pathways contribute mainly to the complement activation against HIV-1.…”

“…Therefore, the development of anti-HIV-1 antibodies with potent complement activation activity may be an important determinant of vaccine-induced immunity to HIV-1 infection. 17 Ab immunity in HIV-1 infection While antibodies activate the complement system and mediate complement-dependent lysis of HIV-1 virions and HIV-1-infected cells, they have other important roles in clearing and neutralizing HIV-1 virions and HIV-1-infected cells. Both neutralizing Abs (nAbs) and non-neutralizing Abs (non-nAbs) can be simultaneously elicited during an effective immune response to viral infection.…”

Critical issues in mucosal immunity for HIV-1 vaccine development

“…37 Thus for a variety of reasons, even with highly immunogenic envelope constructs, the human B-cell arm of the immune system prefers to not recognize the vulnerable region epitopes of the HIV-1 envelope but rather prefers to recognize regions of the envelope that induce nonneutralizing antibodies. 38 , 39 A number of other types of anti-HIV-1 antibody responses could potentially help control HIV-1 if they were present at the time of transmission, including antibodies that aggregate virions, thus preventing virion movement across mucosal epithelia 40 ; inhibit transcytosis 41 ; fix complement and lyse virions 42 ; inactivate virus through macrophage Fc-mediated uptake; and mediate antibody-dependent cellular cytotoxicity (ADCC). 43 The latter response might be critically important for targeting infected cells because neutralizing antibodies might be inefficient at preventing viral cell-cell transmission.…”