Host-Induced Changes in Infectivity of Friend Spleen Focus-Forming Virus2

To study the nature of murine leukemia virus “adaptation” to a different host strain, the infective properties of a member of the Friend virus complex, spleen focus-forming virus (SFFV), were examined in terms of: 1) host range, 2) neutralization kinetics, and 3) titration dose-response curves for “hitness.” SFFV-S, virus maintained in Swiss mice, was passaged through newborn BALB/c mice. After 3 serial passages, the recovered virus, called SFFV-B, differed in host range from SFFV-S as measured by the spleen focus assay method. Despite increased infectivity of SFFV-B in BALB/c and A mice, there was no detectable antigenic difference between SFFV-B and SFFV-S when compared by their neutralization kinetics with rabbit antisera directed against normal Swiss or BALB/c tissue. However, titration of SFFV-S in BALB/c mice yielded a multiple-hit, dose-response curve, whereas titration of SFFV-B in BALB/c mice and of SFFV-S in Swiss mice gave one-hit, dose-response relationships. In addition, SFFV-S gave a one-hit dose-response curve in BALB/c mice coinfected with a lymphatic leukemia virus (LLV-S) isolated in Swiss mice from Friend virus complex and free of detectable SFFV. Passage of LLV-S through newborn BALB/c mice yielded virus (LLV-B), with significantly increased helper activity. The data provide strong evidence that SFFV, as expressed in BALB/c mice, is defective, in that an associated virus particle, LLV, is required in addition to SFFV for spleen focus formation. Thus “adaptation” of SFFV in BALB/c mice results from an increased titer of SFFV associated with LLV that can express its helper activity in the BALB/c strain.