Structure and Variations of Feline Immunodeficiency Virus Envelope Glycoproteins

doi:10.1006/viro.1993.1083

Virology

Volume 192, Issue 2, February 1993, Pages 659-662

https://doi.org/10.1006/viro.1993.1083 Get rights and content

Abstract

We report the characterization of the env gene of a feline immunodeficiency virus isolate from France (FIV Wo). FIV Wo gag and env genes were cloned directly from cat peripheral blood mononuclear cells, using polymerase chain reaction. The env molecular clone was shown to be functional and to express antigenically relevant envelope glycoproteins in vitro. Alignment of FIV Wo sequences with available FIV sequences and application of a regionalization algorithm resulted in delineation of variable and conserved domains of FIV Env. These data were used to build a schematic folding model of FIV envelope glycoproteins. The Env molecular clone, variability map, and structural model constitute helpful tools for future studies of FIV envelope aimed at the determination of structure-function relationships or design of diagnostics or vaccine reagents.

References (0)

Cited by (84)

Differences in Env and Gag protein expression patterns and epitope availability in feline immunodeficiency virus infected PBMC compared to infected and transfected feline model cell lines
2017, Virus Research
Env and Gag are key components of the FIV virion that are targeted to the plasma membrane for virion assembly. They are both important stimulators and targets of anti-FIV immunity. To investigate and compare the expression pattern and antigenic changes of Gag and Env in various research models, infected PBMC (the natural FIV host cells) and GFox, and transfected CrFK were stained over time with various Env and Gag specific MAbs. In FIV infected GFox and PBMC, Env showed changes in epitope availability for antibody binding during processing and trafficking, which was not seen in transfected CrFK. Interestingly, epitopes exposed on intracellular Env and Env present on the plasma membrane of CrFK and GFox seem to be hidden on plasma membrane expressed Env of FIV infected PBMC. A kinetic follow up of Gag and Env expression showed a polarization of both Gag and Env expression to specific sites at the plasma membrane of PBMC, but not in other cell lines. In conclusion, mature trimeric cell surface expressed Env might be antigenically distinct from intracellular monomeric Env in PBMC and might possibly be unrecognizable by feline humoral immunity. In addition, Env expression is restricted to a small area on the plasma membrane and co-localizes with a large moiety of Gag, which may represent a preferred FIV budding site, or initiation of virological synapses with direct cell-to-cell virus transmission.
Phylogenetic analysis of feline immunodeficiency virus strains from naturally infected cats in Belgium and The Netherlands
2015, Virus Research
Citation Excerpt :
They originated from geographically distinct parts of Belgium and The Netherlands. Two samples, BEWVkhde and BEHEramo, formed a cluster together with the French isolate Wo (Pancino et al., 1993). All other 32 samples had an identical gag sequence, and clustered together with the San Diego isolate FIV PPR (Phillips et al., 1990).
Feline immunodeficiency virus (FIV) is a major pathogen in feline populations worldwide, with seroprevalences up to 26%. Virus strains circulating in domestic cats are subdivided into different phylogenetic clades (A–E), based on the genetic diversity of the V3-V4 region of the env gene. In this report, a phylogenetic analysis of the V3-V4 env region, and a variable region in the gag gene was made for 36 FIV strains isolated in Belgium and The Netherlands. All newly generated gag sequences clustered together with previously known clade A FIV viruses, confirming the dominance of clade A viruses in Northern Europe. The same was true for the obtained env sequences, with only one sample of an unknown env subtype. Overall, the genetic diversity of FIV strains sequenced in this report was low. This indicates a relatively recent introduction of FIV in Belgium and The Netherlands. However, the sample with an unknown env subtype indicates that new introductions of FIV from unknown origin do occur and this will likely increase genetic variability in time.
Isolation and partial characterization of Brazilian samples of feline immunodeficiency virus
2011, Virus Research
Citation Excerpt :
The env gene encodes surface and transmembrane glycoproteins and is highly variable (Olmsted et al., 1989; Talbott et al., 1989; Greene et al., 1993). Within the env gene, nine variable regions have been defined, separated by more conserved regions (Pancino et al., 1993b). On the basis of analyses of env variable regions V3–V5, FIV has been classified into five subtypes (A–E) and recombinant strains (Sodora et al., 1994; Kakinuma et al., 1995; Pecoraro et al., 1996) the number of subtypes may increase as further studies reveal additional diversity.
Feline immunodeficiency virus (FIV) causes a slow progressive degeneration of the immune system which eventually leads to a disease comparable to acquired immune deficiency syndrome (AIDS) in humans. FIV has extensive sequence variation, a typical feature of lentiviruses. Sequence analysis showed that diversity was not evenly distributed throughout the genome, but was greatest in the envelope gene, env. The virus enters host cells via a sequential interaction, initiated by the envelope glycoprotein (env) binding the primary receptor molecule CD134 and followed by a subsequent interaction with chemokine co-receptor CXCR4. The purpose of this study was to isolate and characterize isolates of FIV from an open shelter in São Paulo, Brazil. The separated PBMC from 11 positive cats were co-cultured with MYA-1 cells. Full-length viral env glycoprotein genes were amplified and determined. Chimeric feline × human CD134 receptors were used to investigate the receptor utilization of 17 clones from Brazilian isolates of FIV. Analyses of the sequence present of molecular clones showed that all clones grouped within subtype B. In contrast to the virulent primary isolate FIV-GL8, expression of the first cysteine-rich domain (CRD1) of feline CD134 in the context of human CD134 was sufficient for optimal receptor function for all Brazilian FIV isolates tested.
Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus
2008, Virus Research
Feline immunodeficiency virus (FIV) is a member of the genus Lentivirus and causes AIDS-like disease in its natural host, the cat. Like other lentiviruses, FIV displays a high degree of nucleotide sequence variability that is reflected in both the geographic distribution of the viruses and the different cat species that are infected. Although a lot of data on sequence variation at the population level is available, relatively little is known about the intrahost variation of FIV sequences. In the present study, cats were infected with either a biological isolate of FIV or a molecular clone that was derived from the same isolate, AM19. After infection, the cats were monitored for up to 3 years and at various time points sequences were obtained of virus circulating in the plasma. Regions of the env gene and the orfA gene were amplified, cloned and their nucleotide sequence analyzed. Furthermore, the extent of sequence variation in the original inocula was also determined. It was found that FIV is displaying relative little sequence variation during infection of its host, both in the env and the orfA gene, especially after infection with molecular clone 19k1. Although the extent of variation was higher after infection with biological isolate AM19, a large portion of these variant sequences was already present in the inoculum.
Molecular mechanisms of FIV infection
2008, Veterinary Immunology and Immunopathology
Feline immunodeficiency virus (FIV) is an important viral pathogen worldwide in the domestic cat, which is the smallest animal model for the study of natural lentivirus infection. Thus, understanding the molecular mechanisms by which FIV carries out its life cycle and causes an acquired immune deficiency syndrome (AIDS) in the cat is of high priority. FIV has an overall genome size similar to HIV, the causative agent of AIDS in man, and shares with the human virus genomic features that may serve as common targets for development of broad-based intervention strategies. Specific targets include enzymes encoded by the two lentiviruses, such as protease (PR), reverse transcriptase (RT), RNAse H, and integrase (IN). In addition, both FIV and HIV encode Vif and Rev elements essential for virus replication and also share the use of the chemokine receptor CXCR4 for entry into the host cell. The following review is a brief overview of the current state of characterization of the feline/FIV model and development of its use for generation and testing of anti-viral agents.
Conservation of inner domain modules in the surface envelope glycoproteins of an ancient rabbit lentivirus and extant lentiviruses and betaretroviruses
2008, Virology
Citation Excerpt :
The model of conservation of the inner domain of lentiviral and betaretroviral SU described here is different from partial or global models of the SU of lentiviruses that were proposed before the HIV-1 gp120 structure was available as a template for model building (Ball et al., 1992; Gallaher et al., 1995; Pancino et al., 1993; Schulz et al., 1992), as previously discussed (Hötzel, 2003; Hötzel and Cheevers, 2000, 2001). In one respect, the model proposed here agrees with previous models: It unifies details of two of these previous models, the amphipathic helices of EIAV and FIV SU (Ball et al., 1992; Pancino et al., 1993), into one conserved structural and functional role that was not previously recognized. The sequence analysis presented here may not describe all the structural similarities between the SU of lentiviruses and even the betaretroviruses.
The consensus sequence of endogenous lentiviral elements in the genome of European rabbits (RELIK) was used to extend a model of conserved lentiviral and betaretroviral surface envelope glycoprotein (SU) inner domain structures. Here it is shown that nearly all the inner domain elements of human and simian immunodeficiency virus gp120 mediating conformational changes upon CD4 binding were conserved in the SU of RELIK. Many of these inner domain elements and a carboxy-terminal region outside the gp120 core are also conserved in the SU of other lentiviruses and betaretroviruses, suggesting conserved mechanisms of SU conformational changes induced by receptor binding.

View all citing articles on Scopus

View full text

Short CommunicationsStructure and Variations of Feline Immunodeficiency Virus Envelope Glycoproteins

Abstract

Short Communications
Structure and Variations of Feline Immunodeficiency Virus Envelope Glycoproteins