SummaryHuman immunodeficiency virus type 1 (HIV-1), in contrast to animal retroviruses such as murine leukemia virus, is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independent of antibody, and C3b deposition facilitates infection of complement receptor-bearing cells. Using gel exclusion chromatography on Sephacryl S-1000, purified virions were found to bind 12sI-1abeled Clq, but not 12SI-labeled dimeric proenzyme Cls. Virions activated the C1 complex, reconstituted from Clq, proenzyme Clr, and 12SI-labeled proenzyme Cls, to an extent comparable with that obtained with immunoglobulin G-ovalbumin immune complexes. To determine the activating viral component, recombinant viral proteins were used: in the solid phase, soluble gp41 (sgp41) (the outer membrane part of gp41, residues 539-684 of gp160) bound Clq, but not dimeric proenzyme Cls, while gp120 was ineffective. In the fluid phase, sgp41 activated the C1 complex in a dose-and time-dependent manner, more efficiently than aggregated Ig, but less efficiently than immune complexes. To localize the C1 activating site(s) in gp41, synthetic peptides (15-residue oligomers spanning amino acids 531-695 of gp160) were used. Peptides covering positions 591-605 and 601-620 and, to a lesser extent, positions 561-575, had both the ability to bind Clq and to induce C3 deposition. These data provide the first experimental evidence of a direct interaction between the C1 complex and HIV-1, and indicate that C1 binding and activation are mediated by specific sites in gp41.

An individual analysis of IgG antibodies against 12 known antigenic domains of human cytomegalovirus (HCMV)-derived structural phospho- and glycoproteins and nonstructural polypeptides was performed. In HCMV-seropositive healthy persons, the separate determination of antibody titers against the various antigens resulted in an antibody profile that was characteristic for each individual. Profiles were qualitatively stable over a period of >4 years. However, quantitative changes were observed in some persons. During primary HCMV infection, a delay of 50-100 days in the appearance of glycoprotein-specific antibodies was observed, whereas immunoglobulins directed against other HCMV-specific antigens were promptly synthesized. In contrast, during reactivation or reinfection, a synchronized production of antibodies was found. Levels of glycoprotein-specific antibodies and detection of viral DNA in peripheral blood inversely correlated. Precursor B cell analyses showed no significant differences between glycoprotein-specific and phosphoprotein-specific B cells.

No abstract