A Single Mutation within the V3 Envelope Neutralization Domain of Feline Immunodeficiency Virus Determines Its

Feline immunodeficiency virus (FIV) isolates differ in the ability to replicate in Crandell feline kidney (CRFK) cells. The difference in tropism between two variants of the Dutch isolate FIV-UT113 was studied by using molecular clones which contained the envelope genes of the variants in a background of the FIV-14 Petaluma sequence. Virus produced from clone pPET-113Th replicated in thymocytes, whereas virus from pPET-113Cr propagated in both thymocytes and CRFK cells, thereby reflecting 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 tropism. Sequence analysis of the ex-changed fragments demonstrated two amino acid changes that led to an increase of the overall charge of the V3 domain: a G3R transition at position 397 and a E3K change at position 407. Mutational analysis of these residues revealed that the E3K shift was responsible for the change in tropism, while the G3R mutation improved the replication kinetics in CRFK cells. Mapping of a tropism determinant for FIV to a region which is also a major neutralization domain is reminiscent of human immunodeficiency virus type 1, in which a similar colocation was found. Feline immunodeficiency virus (FIV) is a lentivirus that causes a slow progressive degeneration of the immune syste