Antiviral antibody reacting on the plasma membrane alters measles virus expression inside the cell

Abstract

SOME viruses are known to persist despite a functional antiviral immune response by the host. For example, measles or measles-like viruses can cause persistent infection in man leading to a progressive degenerative disease, subacute sclerosing panencephalitis (SSPE), characterised by unusually high titres of measles virus antibodies in serum and cerebral spinal fluids (see refs 1, 2 for reviews). Peripheral blood lymphocytes specifically responsive to measles virus antigens are generated and lyse target cells expressing virus antigens on their surfaces3,4. Sera from SSPE patients enhance rather than block or suppress immunologically mediated killing3−5. But although this antimeasles virus immune response is vigorous, the virus infection does not terminate because one can detect virus antigens and isolate infectious virus from central nervous system and lymphoid tissues1. To explain this we postulated that antibody to measles virus modulates or strips viral antigens off surfaces of virus infected cells6–7. This contention is based on the finding that specific measles antibody added to cultured infected cells modulate viral antigens on the cells' surfaces6. These cells then express less viral antigens on their surfaces and thereby avoid the host's immune assault. Cells denuded of viral antigens on their surfaces resist antibody and complement-mediated or immune lymphocyte-mediated killing6,7 yet retain viral genetic information6. Further, during antibody modulation in vitro, the numbers of viral nucleocapsids accumulated inside the cell dramatically increase and are positioned randomly6. This in vitro picture closely resembles the distribution of nucleocapsids in cells obtained by biopsy from patients with SSPE1,8,9. Quantitatively, about 10- to 50-fold less antibody is needed on the surfaces of infected cells to modulate viral antigens than is needed to activate the complement system leading to immune lysis of infected cells5,10. To clarify the molecular events occurring during antibody-induced antigenic modulation, we have studied measles virus antibody bound to the surfaces of infected cells and ascertained what alterations occur within these cells. Here we report that measles virus antibodies added to virus infected HeLa cells decrease the content of both viral structural polypeptide haemolysin expressed on the cell surface and a structural polypeptide (measles virus phosphoprotein, P) found inside the cell. These observations indicate that antibody directed against an antigen on the cell surface can interfere with viral proteins expressed inside the cell. Because phosphoprotein seems to form complexes with the nucleocapsid, our findings may offer leads towards understanding viral regulation during persistence. We also note that three measles virus polypeptides—P, nucleocapsid (NC) and matrix protein (M)—are phosphorylated.