Additional uncharacterized proteins critical to HIV replication must differ between mouse and humans, Goldstein surmises. The mouse model had seemingly hit another wall. That wall provides the reason that HIV, unlike other viruses, has been so hard to model, notes Goldsmith. HIV has a very strict host range, and human tissues are highly susceptible. The mouse in particular may have a tough time getting past the wall of permissiveness, because, as Goldstein notes, it blocks infection at multiple levels.
Blocks exist at both the entry and postentry levels.
Getting around them will likely take massive manipulation. Goldstein's team is attacking the permissiveness problem from a number of angles. First, the researchers are trying to express the CD4 and CCR5 transgenes at higher levels in a greater variety of cells, including monocytes, dendritic cells, and T cells. And finally, they've generated a mouse that is transgenic for a full-length HIV genome. With the exception of the last approach, Goldstein's team is focusing on entry issues.