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.

Selective Expansion of Viral Variants following Experimental Transmission of a Reconstituted Feline Immunodeficiency Virus Quasispecies

“…Previous data have suggested that the neutralising response to the GL8 strain of FIV develops very slowly [28]. In this study, we could find no evidence to suggest that virus neutralising antibodies played a significant role in the control of the GL8 strain of FIV during the first 21 weeks of infection.…”

“…In this study, we could find no evidence to suggest that virus neutralising antibodies played a significant role in the control of the GL8 strain of FIV during the first 21 weeks of infection. Potent neutralising responses have been observed in chronically infected cats (reviewed in [28]), however this response may be focussed to a limited number of determinants on Env such as the V4 and V5 loops and escape from neutralisation has been observed [15], [43]–[47]. Using HIV(FIV) pseudotypes bearing the Env proteins from each of the viral variants within the inoculum we established that the strains that replicated weakly in vivo were not targeted selectively by neutralising antibodies during the 21 week study period.…”

“…In previous studies, we followed experimental infection of cats with a molecular clone of GL8 for a period of six years [5], [28]. At the end of the study, we observed the establishment of pools, or “swarms” of viral variants, each with distinct receptor usages and sensitivities to neutralising antibodies [15], [29].…”

Recognition of the Different Structural Forms of the Capsid Protein Determines the Outcome following Infection with Porcine Circovirus Type 2

“…Classic examples of immunological decoys are found in lentiviruses, such as feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV). As reviewed by Hosie et al (13), the variable regions V3, V4, and V5 of the envelope (Env) protein of FIV are essential for virus infection, are immunodominant, and are targets for neutralization by antibody. However, continuous variation, as a result of shortening, lengthening, and/or peptide sequence hypervariability, produces large quantities of antibodies that are nonprotective.…”

Feline Immunodeficiency Virus (FIV) Infection in Cats: A Possible Cause of Renal Pathological Changes

“…The binding site remains largely hidden and is therefore inaccessible for mentioned antibody. Whereas overall HIV and FIV Env structure is maintained [7], HIV uses various coreceptors, including a range transmembrane domain G-protein-coupled receptors. In Despite detailed knowledge of most clinicopathological features during FIV infection, information on renal involvement is limited.…”