Antibody-Independent Neutralization of Vesicular Stomatitis Virus by Human Complement: II. Formation of VSV-Lipoprotein Complexes in Human Serum and Complement-Dependent Viral Lysis

Vesicular stomatitis virus (VSV) is efficiently neutralized by normal, nonimmune human serum without the participation of antibody. Neutralization is complement-(C) dependent and requires the early-acting components of the classical pathway, C1, C4, C2, and C3, but not later-acting C components. In further studies, normal human serum was found to markedly increase the density of a variable but significant proportion of virus-associated RNA and to markedly decrease the density of the remainder of virus-associated RNA. The RNA of increased density was found to be dense ribonucleocapsid cores released from VSV by C-dependent viral lysis mediated through the classical pathway. The released ribonucleocapsid cores found at the bottom of sucrose density gradients after incubation of VSV with human serum were resistant to degradation by proteolytic enzymes. The VSV-derived RNA found floating on the tops of sucrose density gradients performed on serum-treated VSV was infectious virus. The decreased density was due to binding of VSV to human serum lipoproteins (LP), primarily very low density lipoproteins (VLDL). Binding of VLDL to VSV required the presence of the viral envelope and the external glycoprotein, G. Despite the binding of LP to VSV, LP did not neutralize VSV, and LP-depleted sera were fully active in neutralizing VSV. Thus, LP do not represent an accessory factor for the C-dependent neutralization of VSV.