Comparison of biological properties of feline immunodeficiency virus isolates using recombinant chimeric viruses

Abstract

The biological properties of homogeneous populations of feline imrnunodeficiency viruses derived from infectious molecular clones of the TM1, TM2 and Petaluma strains were compared. Differences in infectivity for Crandell feline kidney (CRFK) cells, and in syncytium formation and replication kinetics in a feline T lymphoblastoid cell line (MYA-1 cells) were observed. To investigate the basis of these differences between the TM2 and Petaluma strains, we first compared the basal promoter activity of the long terminal repeat which is a highly divergent region, but no significant difference in activities was found in CRFK cells. We then constructed two recombinant chimeric clones which carry gag, pol, v/f and ORF A from the heterologous virus. From analyses using the chimeric clones, it was revealed that efficient virus growth in CRFK cells and MYA-1 cells was regulated by the gag, pol, vif and ORF A regions, whereas viral determinants of infectivity for CRFK cells, and syncytium formation and cytopathogenicity in MYA-1 cells, were located in the env region.

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3

“…4). However, FIV subtype B circulates in the wild (26, 35–37), and strains of this subtype, including strain TM2, infect and replicate in certain feline cell lines (e.g., MYA-1 cells) expressing endogenous A3 genes (38). Our findings, together with previous observations, suggest the ability of FIV to circumvent feline A3-mediated antiviral effects independently of Vif.…”

“…Therefore, FIV subtype B appears to be relatively less pathogenic. Moreover, cell-based experiments have revealed that the level of growth of FIV strain TM2 in a feline CD4 + T-cell line expressing endogenous A3 genes is significantly lower than that of strain Petaluma (19, 38), and this difference in viral growth is determined by specific viral genes, such as gag , pol , and vif (38). The relatively lower replication capacity of FIV strain TM2 in cells expressing A3 is likely attributable to the attenuation of Vif.…”

Strain.

“…FIV Petaluma strain which was first isolated in the United States from a cat developing AIDS-like diseases is classified as subtype A [31,38,44]. TM1 and TM2 strains isolated in Japan are classified as subtype B and considered to have milder pathogenicity in vitro and in vivo when compared with subtype A virus [2,20,24,42].…”

Experimental Mucosal Infection with Molecularly Cloned Feline Immunodeficiency Viruses

“…They have been shown to use CXCR4 alone to infect the CRFK cells (25,30,31); however, the receptor(s) used to infect lymphoid cells remains controversial (9,10,12,17,26). Similar to HIV type 1, FIV has considerable sequence variation in the env gene, and the third to fifth variable regions (V3-V5) of the env gene contain an immunodominant neutralization domain and a determinant of CRFK tropism (15,17,29). Chimeric and sequencing analyses of the env gene of the CRFK-tropic viruses suggest that the principal determinant of the CRFK tropism resides in the V3 loop of the surface unit Env protein (29).…”

“…The strain TM2 belongs to clade B (23) and infects and proliferates well in feline lymphocytes but not CRFK cells (15). Ten micrograms of each plasmid was transfected into CRFK cells by the calcium phosphate coprecipitation method.…”