Interaction of Ross River Virus with the Complement System

Abstract

SUMMARYIn the absence of virus-specific antibody, Ross River virus failed to activate either the classical or alternative complement pathways. Instead, it inhibited the cleavage of C3 via both pathways. The virus did not appear to act by disrupting C3bBb complexes or by preventing cleavage of factor B by factor D. Instead Ross River virus was found to interfere with the actual cleavage of C3 by activated factor B (C3bBb) of the alternative pathway and C4b2a of the classical pathway.

Interaction of Alphaviruses with the serum complement system is a function of method of purification

“…In contrast, Ross River (grown in PS-EK [1] or C6-36 cells) and Sindbis viruses purified on sodium potassium tartrate gradients inhibited the spontaneous cleavage of C 3 in serum.…”

“…It has also extended and reconciled two apparently contradictory reports [1,7] of the effects of Alphaviruses on the complement system, by demonstrating that while Sindbis virus may activate the alternate complement pathway in non-immune serum, Ross River virus, irrespective of the mode of purification, appears to lack this capacity.…”

“…The C 6-36 line of Aedes albopictus mosquito cells [1][2][3][4][5][6][7][8] was infected with a fifth passage suckling mouse brain preparation of Sindbis virus (MRM 39) or Ross River virus (T 48) in RPM 1 1640 (Commonwealth Serum Laboratories, Australia) supplemented with 0.02% w/v bovine serum albumin (BSA; Sigma, U.S.A.). Seventy-two hours postinfection, culture supernate was recovered, cell debris removed by centrifugation at 10,000 g for 30 min, and virus pelleted at 10,000g for 16 hours at 4 °C.…”

“…Similar experiments with Ross River virus failed to produce any cleavage of C 3. Instead, Ross River virus inhibited a cleavage of C 3 by C 142 in the classical complement pathway and C 3 bBb in the alternate pathway [1].…”

“…Two recent in vitro studies of the interaction of Alphaviruses with the serum complement system have produced completely different results [1,6,7]. Incubation of Sindbis virus with non-immune serum resulted in cleavage of complement component C 3 as a result of alternate complement pathway activation by the virus [6,7].…”