THE ROLE OF REPLICATION-COMPETENT VIRUS IN FRIEND VIRUS DISEASE

Abstract

Friend virus complex (FV), which consists of the replication-competent Friend murine leukemia virus (FMuLV) and the replication-defective spleen focus-forming virus (SFFV), induces a multistage erythroleukemia. We have examined the role of the replication-competent helper virus in the early and late stages of FV disease by replacing FMuLV, the native helper, with Akv, the endogenous ecotropic MuLV of AKR mice. SFFV{dollar}\sb{lcub}\rm P{rcub}{dollar}/FRE, an established fibroblast line nonproductively infected with the polycythemic strain of SFFV, was superinfected with FMuLV or with Akv. Although supernatants from these cells contained equal amounts of helper virus, supernatants from Akv-infected SFFV{dollar}\sb{lcub}\rm P{rcub}{dollar}/FRE cells show 100-5000-fold less activity than those from FMuLV-infected cells with respect to spleen focus induction in vivo. Since virions isolated from these two supernatants contain similar amounts of genomic RNA, it does not appear that the difference is due to a relative inability of Akv to package SFFV. Although FMuLV- and Akv-rescued SFFV are equally infectious in a mouse fibroblast cell line (NIH3T3), FMuLV-rescued SFFV is far more efficient in causing a productive infection in vitro of BFU-e cells, the target cell of FV disease. In vivo studies showed that FMuLV injected with helper-free SFFV induces 50-500 fold more splenic foci than Akv coinjected with helper-free SFFV.;Helper virus also affects mortality rates that reflect the late stage of the disease. When FMuLV- or Akv-rescued SFFV was injected into NIH Swiss mice at dosage levels adjusted to give equal numbers of spleen foci, all of the mice receiving FMuLV-rescued SFFV developed splenomegaly and died, whereas none of the mice receiving Akv-rescued SFFV died or developed detectable splenomegaly. When FMuLV was coinjected with Akv-rescued SFFV, the mortality rate rose from 0% to 100%. Similarly, although injection of helper-free SFFV alone did not induce any mortality, coinjection of helper-free SFFV with FMuLV or with a high titer of Akv resulted in 100% mortality. Thus, helper virus used to rescue SFFV plays at least a quantitatively important role in the early stage of FV disease and a crucial role in the late stage of the disease in vivo.