A SINGLE MUTATION WITHIN THE V3 ENVELOPE NEUTRALIZATION DOMAIN OF FELINE IMMUNODEFICIENCY VIRUS DETERMINES ITS TROPISM FOR CRFK CELLS

Feline immunodeficiency virus (FIV) isolates differ in the ability to replicate in Crandell feline kidney (CRFK) cells, The difference in tr opism between two variants of the Dutch isolate FIV-UT113 was studied by using molecular clones which contained the envelope genes of the va riants in a background of the FIV-14 Petaluma sequence. Virus produced from clone pPET-113Th replicated in thymocytes, whereas virus from pP ET-113Cr propagated in both thymocytes and CRFK cells, thereby reflect ing the phenotypes of the parental variants. Exchange of envelope gene fragments showed that a 464-bp surface protein (SU)-encoding fragment encompassing the third variable region (V3) determines CRFK cell trop ism. Sequence analysis of the exchanged fragments demonstrated two ami no acid changes that led to an increase of the overall charge of the V 3 domain: a G-->R transition at position 397 and a E-->K change at pos ition 407. Mutational analysis of these residues revealed that the E-- >K shin was responsible for the change in tropism, while the G-->R mut ation improved the replication kinetics in CRFK cells, Mapping of a tr opism determinant for FIV to a region which is also a major neutraliza tion domain is reminiscent of human immunodeficiency virus type 1, in which a similar colocation was found.