No abstract

Human rhinovirus type 2 did not replicate in nonpermissive mouse cells; the restriction was not in adsorption but in the early events of virus replication. Mutants which had been adapted to grow in mouse cells had the following characteristics: (i) no change in the structural protein, (ii) a larger nonstructural protein and its precursor protein, and (iii) an altered viral RNA synthesis. The altered nonstructural proteins correlated with a change in host range of the virus and may be involved in viral RNA synthesis.

2335 SUMMARYWe describe here a mouse model for rhinovirus infection using a variant of human rhinovirus type 2 (HRV2/H) which replicated 50-to 300-fold in the lungs of BALB/c mice. The variant virus differed only marginally from HRV2/H according to various biochemical parameters. Use of a photosensitive inoculum and pretreatment of the animals with actinomycin D were necessary for detection of reproducible and significant levels of virus replication. This mouse model of rhinovirus infection is the first example of human rhinovirus replication in a non-primate mammal, and provides an important link for the development of rhinovirus therapy or prophylaxis.

Human rhinovirus 39 (HRV39) is blocked in nonpermissive L cells at both adsorption and intracellular replication steps. We have selected a host range variant of HRV39 capable of bypassing the intracellular replication block and found it to have altered nonstructural P2 proteins. These alterations are similar to those reported earlier for host range variants of HRV2 (F. H. Yin and N. B. Lomax, J. Virol. 48:410-418, 1983). This observation suggests that the intracellular replication block for both HRV2 and HRV39 in mouse L cells is at the same step. We propose that the P2 protein is an essential viral component that cannot function in mouse L cells unless altered. This alteration occurs spontaneously in stocks of HRV39 during growth in permissive HeLa cells.