Differential cell tropism of feline immunodeficiency virus molecular clones in vivo

Independent studies have demonstrated different cell tropisms for molecular clones of feline immunodeficiency virus (FIV). In this report, we examined three clones, FIV-pF34, FIV-14, and FIV-pPPR, for replication in Crandell feline kidney (CrFK) cells, feline peripheral blood mononuclear cells (PBMC ), and feline macrophage cultures. Importantly, cell tropism far these thre e clones was also examined in vivo. FIV-pF34 replication was efficient in C rFK cells but severely restricted in PBMC, whereas replication of FIV-pPPR was vigorous in PBMC but severely restricted in CrFK cells, FIV-14 replicat ion was productive in both CrFK cells and PBMC. Interestingly, all three mo lecular clones replicated with similar efficiencies in primary feline monoc yte-derived macrophages. In vivo, FIV-pF34 proved least efficient for estab lishing persistent infection, and proviral DNA when detectable, was localiz ed predominately to nonlymphoid cell populations (macrophages). FIV-pPPR pr oved most efficient for induction of a persistent viremia in vivo, and prov iral DNA was localized predominately in CD4(+) and CD8(+) lymphocyte subset s. FIV-14 inoculation of cats resulted in an infection characterized by ser oconversion and localization of proviral DNA in CD4(+) lymphocytes only. Re sults of this study on diverse FIV molecular clones revealed that in vitro replication efficiency of an FN isolate in PBMC directly correlated with re plication efficiency in vivo, whereas proficiency for replication in macrop hages in vitro aas not predictive for replication potential in vivo. Also, infection of both CD4(+) and CD8(+) lymphocyte subsets was associated with higher virus load in vivo. Results of the studies on these three FN clones, which exhibited differential cell tropism, indicated a correlation between in vitro and in vivo cell tropism and virus replication.