Willi, B. et al. (2016) non-epizootic infection associated with skin ulceration and edema are presented. 32Samples from eleven symptomatic cats, four in-contact cats and 27 cats with no 33 contact with symptomatic cats were collected and tested for FCV, feline herpesvirus-34
BackgroundIn the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.ResultsFollowing infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.ConclusionsThe FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.
BackgroundFeline calicivirus (FCV) is a common cause of upper respiratory tract disease in cats worldwide. Its characteristically high mutation rate leads to escape from the humoral immune response induced by natural infection and/or vaccination and consequently vaccines are not always effective against field isolates. Thus, there is a need to continuously investigate the ability of FCV vaccine strain-induced antibodies to neutralize field isolates.MethodsSeventy-eight field isolates of FCV isolated during the years 2008–2012 from Swedish cats displaying clinical signs of upper respiratory tract disease were examined in this study. The field isolates were tested for cross-neutralization using a panel of eight anti-sera raised in four pairs of cats following infection with four vaccine strains (F9, 255, G1 and 431).ResultsThe anti-sera raised against F9 and 255 neutralised 20.5 and 11.5 %, and 47.4 and 64.1 % of field isolates tested, respectively. The anti-sera against the more recently introduced vaccine strains G1 and 431 neutralized 33.3 and 70.5 % and 69.2 and 89.7 %, respectively. Dual vaccine strains displayed a higher cross-neutralization.ConclusionsThis study confirms previous observations that more recently introduced vaccine strains induce antibodies with a higher neutralizing capacity compared to vaccine strains that have been used extensively over a long period of time. This study also suggests that dual FCV vaccine strains might neutralize more field isolates compared to single vaccine strains. Vaccine strains should ideally be selected based on updated knowledge on the antigenic properties of field isolates in the local setting, and there is thus a need for continuously studying the evolution of FCV together with the neutralizing capacity of vaccine strain induced antibodies against field isolates at a national and/or regional level.Electronic supplementary materialThe online version of this article (doi:10.1186/s13028-015-0178-z) contains supplementary material, which is available to authorized users.
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.
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