Cell-free infectivity of HIV type 1 produced in nonpermissive cells is only moderately impacted by C-terminal Env truncation despite abrogation of viral spread.

Mutant HIV virions, encoding C-terminally truncated Env proteins, exhibit a cell-specific replication defect, i.e., they can replicate in a few T cell lines (termed permissive cells) but not in the majority of T cell lines (termed nonpermissive cells). We have studied the properties of two mutant virions (pNL-Tr712 and pNL-Tr752), encoding Envs with C-terminal truncations of 144 and 104 amino acids, respectively. We show that although unable to give rise to a spreading infection in nonpermissive H9 cells, both cell-free pNL-Tr712 and pNL-Tr752 virions, produced in these cells, still exhibit relatively high levels of infectivity (30-80% of wildtype) when tested in nonpermissive target cells. Compatible with this high remaining infectivity, we observed that the levels of Env incorporation into mutant virions, produced in nonpermissive cells, were not drastically reduced as has been reported by others. The high remaining infectivity of cell-free mutant virions in nonpermissive cells is difficult to reconcile with the complete lack of spreading infection in these cells. We demonstrate that nonpermissive cells are less susceptible to single-round infection with cell-free virus than permissive cells. It is thus conceivable that in these cells other transmission routes, e.g., cell-cell transmission, may be more important for total virus spread and that this route may be more severely impacted by the C-terminal Env truncations.