Feline immunodeficiency virus (FIV) neutralization: a review

Abstract

One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env), a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3) of Env. For feline immunodeficiency virus (FIV), as well as the related human immunodeficiency virus-1 (HIV-1), little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1.

Keywords: FIV; feline immunodeficiency virus; neutralization; neutralizing antibody.

Figure 1.

Longitudinal development of virus neutralizing ant ibodies in feline immunodeficiency virus (FIV)-infected cats. Sequential plasma samples collected from three cats (A,B—611, C,D—612, E,F—613) infected experimentally with a molecular clone of FIV GL8 were diluted 1:10 and examined for ability to neutralize HIV (FIV) pseudotypes bearing the GL8 Env as described [35]. Luciferase activity (A,C,E) was measured at three days post-infection and the percentage neutralization (B,D,F) calculated relative to a “no plasma” control. Each point is derived from the mean (n = 3) +/− SEM.

Figure 2.

Relationship between estimated age and ability to neutralize FIV. 214 plasma samples from cats testing positive for FIV in the United Kingdom were diluted 1:10 and tested for ability to neutralize GL8 Env-bearing pseudotypes. Graph represents estimated age versus percentage neutralization relative to a no plasma control.

Figure 3.

Amino acid sequence variation in the V5 loop of viral variants isolated from a GL8-infected cat. Five years post-infection with a molecular clone of GL8, variants were isolated that were either sensitive (+) or resistant (−) to virus neutralizing antibody. Variants that were sensitive to homologous VNA had identical V5 sequences. (Adapted from [52]).