Feline Immunodeficiency Virus Strains Research Articles

Molecular survey of feline immunodeficiency virus (FIV) infection in Namibian cats

Feline Immunodeficiency Virus (FIV) is one of the most important infectious diseases of cats, with potential implications in wildlife conservation. Unfortunately, FIV screening and surveillance in domestic cats remains limited in several African countries, including Namibia. In this study, 279 blood samples from domestic cats in Namibia were analyzed for FIV diagnosis by PCR. The cats represented various regions and were cared for by people largely from rural areas with limited financial means. Only 1.43 % of the samples tested positive, unexpectedly low given their outdoor lifestyles. The infected cats, primarily adult and unsterilized, showed no typical FIV symptoms, suggesting subclinical infections. Genetic analysis of the detected strains indicated a unique FIV strain cluster in Namibia, although with a certain within-country variability, in the absence of consistent geographical clustering. The present study represents the first detection and genetic characterization of FIV in the Namibian domestic cat population. Although the infection frequency was low, also in the rural free-roaming population, the features of the enrolled population could have biased the estimation, suggesting the need for more extensive surveys involving diseased and older cats as well. Additionally, because of the long-lasting subclinical nature of the infection, frequent monitoring activities should be performed that allow prompt isolation of infected animals and the implementation of appropriate control measures if necessary.

The effects of Avemar treatment on feline immunodeficiency virus infected cell cultures.

In addition to standard highly active antiretroviral therapy protocols, complementary therapies using natural compounds are widely used by human immunodeficiency virus (HIV)-infected human patients. One such compound is the fermented wheat germ extract (FWGE), named Avemar. In this study, we investigate the effects of Avemar in a feline-acquired immunodeficiency syndrome model. MBM lymphoid cells were acutely infected by the American feline immunodeficiency virus (FIV)-Petaluma (FIV-Pet) and the European FIV Pisa-M2 strains. FL-4 lymphoid cells, continuously producing FIV-Pet, served as a model for chronic infection. Crandell Rees feline kidney (CRFK) cells were infected by either FIV-Pet or feline adenovirus (FeAdV) as a model for transactivation and opportunistic viral infection. Cell cultures were treated pre- and post-infection with serial dilutions of spray-dried FWGE (Avemar pulvis, AP), a standardized active ingredient in commercial Avemar products. Residual FIV and FeAdV infectivity was quantified. In a concentration-dependent manner, AP inhibited replication of FIV strains in MBM and CRFK cells by 3-5log. Low AP concentration prevented FIV-Pet release from FL-4 cells. Higher concentrations destroyed virus-producing cells with cytopathic effects resembling apoptosis. AP strongly inhibited FeAdV production inside CRFK cells but not in HeLa cells. Adenovirus particles are then released via the disintegration of CRFK cells. This report is the first to describe the antiviral effects of Avemar. Further studies are required to confirm its in vitro and in vivo effects and to investigate the potential for its use as a nutraceutical in FIV-infected felines or HIV-infected humans. Avemar, as a single nutraceutical, inhibits FIV replication and destroys retrovirus carrier cells. An important conclusion is that prolonged Avemar treatment might reduce the number of retrovirus-producing cells in the host.

Expression of APOBEC3 Lentiviral Restriction Factors in Cats.

Feline immunodeficiency virus (FIV) is a naturally occurring T-cell tropic lentiviral disease of felids with many similarities to HIV/AIDS in humans. Similar to primate lentiviral-host interactions, feline APOBEC3 (A3) has been shown to inhibit FIV infection in a host-specific manner and feline A3 degradation is mediated by FIV Vif. Further, infection of felids with non-native FIV strains results in restricted viral replication in both experimental and naturally occurring infections. However, the link between molecular A3-Vif interactions and A3 biological activity during FIV infection has not been well characterized. We thus examined expression of the feline A3 genes A3Z2, A3Z3 and A3Z2-Z3 during experimental infection of domestic cats with host-adapted domestic cat FIV (referred to as FIV) and non-adapted Puma concolor FIV (referred to as puma lentivirus, PLV). We determined A3 expression in different tissues and blood cells from uninfected, FIV-infected, PLV-infected and FIV/PLV co-infected cats; and in purified blood cell subpopulations from FIV-infected and uninfected cats. Additionally, we evaluated regulation of A3 expression by cytokines, mitogens, and FIV infection in cultured cells. In all feline cells and tissues studied, there was a striking difference in expression between the A3 genes which encode FIV inhibitors, with A3Z3 mRNA abundance exceeding that of A3Z2-Z3 by 300-fold or more. Interferon-alpha treatment of cat T cells resulted in upregulation of A3 expression, while treatment with interferon-gamma enhanced expression in cat cell lines. In cats, secondary lymphoid organs and peripheral blood mononuclear cells (PBMC) had the highest basal A3 expression levels and A3 genes were differentially expressed among blood T cells, B cells, and monocytes. Acute FIV and PLV infection of cats, and FIV infection of primary PBMC resulted in no detectable change in A3 expression with the exception of significantly elevated A3 expression in the thymus, the site of highest FIV replication. We conclude that cat A3 expression is regulated by cytokine treatment but, by and large, lentiviral infection did not appear to alter expression. Differences in A3 expression in different blood cell subsets did not appear to impact FIV viral replication kinetics within these cells. Furthermore, the relative abundance of A3Z3 mRNA compared to A3Z2-Z3 suggests that A3Z3 may be the major active anti-lentiviral APOBEC3 gene product in domestic cats.

Utilization of Feline ELISpot to Evaluate the Immunogenicity of a T Cell-Based FIV MAP Vaccine.

The prototype and the commercial dual-subtype feline immunodeficiency virus (FIV) vaccines conferred protection against homologous FIV strains as well as heterologous FIV strains from the vaccine subtypes with closely related envelope (Env) sequences. Such protection was mediated by the FIV neutralizing antibodies (NAbs) induced by the vaccines. Remarkably, both prototype and commercial FIV vaccines also conferred protection against heterologous FIV subtypes with highly divergent Env sequences from the vaccine strains. Such protection was not mediated by the vaccine-induced NAbs but was mediated by a potent FIV-specific T-cell immunity generated by the vaccines (Aranyos et al., Vaccine 34: 1480-1488, 2016). The protective epitopes on the FIV vaccine antigen were identified using feline interleukin-2 (IL-2) and interferon-γ (IFNγ) ELISpot assays with overlapping FIV peptide stimulation of the peripheral blood mononuclear cells (PBMC) from cats immunized with prototype FIV vaccine. Two of the protective FIV peptide epitopes were identified on FIV p24 protein and another two protective peptide epitopes were found on FIV reverse transcriptase. In the current study, the multiple antigenic peptides (MAPs) of the four protective FIV peptides were combined with an adjuvant as the FIV MAP vaccine. The laboratory cats were immunized with the MAP vaccine to evaluate whether significant levels of vaccine-specific cytokine responses can be generated to the FIV MAPs and their peptides at post-second and post-third vaccinations. The PBMC from vaccinated cats and non-vaccinated control cats were tested for IL-2, IFNγ, and IL-10 ELISpot responses to the FIV MAPs and peptides. These results were compared to the results from CD4+ and CD8+ T-cell proliferation to the FIV MAPs and peptides. Current study demonstrates that IL-2 and IFNγ ELISpot responses can be used to detect memory responses of the T cells from vaccinated cats after the second and third vaccinations.

Evaluating the Diversity of the Feline Immunodeficiency Virus (FIV): A Leopard Perspective

To obtain more insights into the prevalence and diversity of species-specific Feline Immunodeficiency Virus (FIV) strains in naturally occurring felid species, 26 leopards (Panthera pardus) from the Kruger National Park (KNP), South Africa, were sampled. Prevalence was determined using a PCR protocol designed to target a 577 bp fragment in the pol-RT gene. Overall prevalence of FIVPpa was estimated at 73%, with no difference in prevalence between male and female leopards. Consistent with previous FIV studies on other felid species, prevalence appears to increase with age (adult = 84%; subadult = 43%). Phylogenetic analyses of these novel sequences were conducted against a revised FIV pol-RT species-specific reference dataset using both Bayesian and maximum likelihood methods. Within FIVPpa two distinct evolutionary groupings are present, which suggests the possibility of geographic variation within FIVPpa and the possibility of distinct subtypes, similar to what has been found in lions (Panthera leo) and domestic cats (Felis catus). The larger FIVPpa dataset provides newinsights into the epidemiology of this under-studied FIV strain and with such high prevalence rates, further studies should focus on immunological and clinical consequences of FIV in wild felids.

Error correction and statistical analyses for intra-host comparisons of feline immunodeficiency virus diversity from high-throughput sequencing data

BackgroundInfection with feline immunodeficiency virus (FIV) causes an immunosuppressive disease whose consequences are less severe if cats are co-infected with an attenuated FIV strain (PLV). We use virus diversity measurements, which reflect replication ability and the virus response to various conditions, to test whether diversity of virulent FIV in lymphoid tissues is altered in the presence of PLV. Our data consisted of the 3′ half of the FIV genome from three tissues of animals infected with FIV alone, or with FIV and PLV, sequenced by 454 technology.ResultsSince rare variants dominate virus populations, we had to carefully distinguish sequence variation from errors due to experimental protocols and sequencing. We considered an exponential-normal convolution model used for background correction of microarray data, and modified it to formulate an error correction approach for minor allele frequencies derived from high-throughput sequencing. Similar to accounting for over-dispersion in counts, this accounts for error-inflated variability in frequencies – and quite effectively reproduces empirically observed distributions. After obtaining error-corrected minor allele frequencies, we applied ANalysis Of VAriance (ANOVA) based on a linear mixed model and found that conserved sites and transition frequencies in FIV genes differ among tissues of dual and single infected cats. Furthermore, analysis of minor allele frequencies at individual FIV genome sites revealed 242 sites significantly affected by infection status (dual vs. single) or infection status by tissue interaction. All together, our results demonstrated a decrease in FIV diversity in bone marrow in the presence of PLV. Importantly, these effects were weakened or undetectable when error correction was performed with other approaches (thresholding of minor allele frequencies; probabilistic clustering of reads). We also queried the data for cytidine deaminase activity on the viral genome, which causes an asymmetric increase in G to A substitutions, but found no evidence for this host defense strategy.ConclusionsOur error correction approach for minor allele frequencies (more sensitive and computationally efficient than other algorithms) and our statistical treatment of variation (ANOVA) were critical for effective use of high-throughput sequencing data in understanding viral diversity. We found that co-infection with PLV shifts FIV diversity from bone marrow to lymph node and spleen.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0607-z) contains supplementary material, which is available to authorized users.

Neutralising antibody response in domestic cats immunised with a commercial feline immunodeficiency virus (FIV) vaccine

Across human and veterinary medicine, vaccines against only two retroviral infections have been brought to market successfully, the vaccines against feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). FeLV vaccines have been a global success story, reducing virus prevalence in countries where uptake is high. In contrast, the more recent FIV vaccine was introduced in 2002 and the degree of protection afforded in the field remains to be established. However, given the similarities between FIV and HIV, field studies of FIV vaccine efficacy are likely to advise and inform the development of future approaches to HIV vaccination.Here we assessed the neutralising antibody response induced by FIV vaccination against a panel of FIV isolates, by testing blood samples collected from client-owned vaccinated Australian cats. We examined the molecular and phenotypic properties of 24 envs isolated from one vaccinated cat that we speculated might have become infected following natural exposure to FIV. Cats vaccinated against FIV did not display broadly neutralising antibodies, suggesting that protection may not extend to some virulent recombinant strains of FIV circulating in Australia.

Selective interaction of heparin with the variable region 3 within surface glycoprotein of laboratory-adapted feline immunodeficiency virus.

Heparan sulfate proteoglycans (HSPG) can act as binding receptors for certain laboratory-adapted (TCA) strains of feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV). Heparin, a soluble heparin sulfate (HS), can inhibit TCA HIV and FIV entry mediated by HSPG interaction in vitro. In the present study, we further determined the selective interaction of heparin with the V3 loop of TCA of FIV. Our current results indicate that heparin selectively inhibits infection by TCA strains, but not for field isolates (FS). Heparin also specifically interferes with TCA surface glycoprotein (SU) binding to CXCR4, by interactions with HSPG binding sites on the V3 loop of the FIV envelope protein. Peptides representing either the N- or C-terminal side of the V3 loop and containing HSPG binding sites were able to compete away the heparin block of TCA SU binding to CXCR4. Heparin does not interfere with the interaction of SU with anti-V3 antibodies that target the CXCR4 binding region or with the interaction between FS FIV and anti-V3 antibodies since FS SU has no HSPG binding sites within the HSPG binding region. Our data show that heparin blocks TCA FIV infection or entry not only through its competition of HSPG on the cell surface interaction with SU, but also by its interference with CXCR4 binding to SU. These studies aid in the design and development of heparin derivatives or analogues that can inhibit steps in virus infection and are informative regarding the HSPG/SU interaction.

Emergence of CD134 cysteine-rich domain 2 (CRD2)-independent strains of feline immunodeficiency virus (FIV) is associated with disease progression in naturally infected cats.

BackgroundFeline immunodeficiency virus (FIV) infection is mediated by sequential interactions with CD134 and CXCR4. Field strains of virus vary in their dependence on cysteine-rich domain 2 (CRD2) of CD134 for infection.FindingsHere, we analyse the receptor usage of viral variants in the blood of 39 naturally infected cats, revealing that CRD2-dependent viral variants dominate in early infection, evolving towards CRD2-independence with disease progression.ConclusionsThese findings are consistent with a shift in CRD2 of CD134 usage with disease progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-014-0095-7) contains supplementary material, which is available to authorized users.

Phylogenetic analysis of feline immunodeficiency virus strains from naturally infected cats in Belgium and The Netherlands

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.

Characterization of Regionally Associated Feline Immunodeficiency Virus (FIV) in Bobcats (Lynx rufus)

Feline immunodeficiency virus (FIV) classically infects felid species with highly divergent species-specific FIVs. However, recent studies have detected an FIV strain infecting both bobcats (Lynx rufus) and pumas (Puma concolor) in California and Florida. To further investigate this observation, we evaluated FIV from bobcats in Florida (n=25) and Colorado (n=80) between 2008 and 2011. Partial viral sequences from five Florida bobcats cluster with previously published sequences from Florida panthers. We did not detect FIV in Colorado bobcats.

Diversity of trends of viremia and T-cell markers in experimental acute feline immunodeficiency virus infection.

ObjectiveThe early events of human immunodeficiency virus infection seem critical for progression toward disease and antiretroviral therapy initiation. We wanted to clarify some still unknown prognostic relationships between inoculum size and changes in various immunological and virological markers. Feline immunodeficiency virus infection could be a helpful model.MethodsViremia and T-cell markers (number of CD4, CD8, CD8βlowCD62Lneg T-cells, CD4/CD8 ratio, and percentage of CD8βlowCD62Lneg cells among CD8 T-cells) were measured over 12 weeks in 102 cats infected with different feline immunodeficiency virus strains and doses. Viremia and T-cell markers trajectory groups were determined and the dose-response relationships between inoculum titres and trajectory groups investigated.ResultsCats given the same inoculum showed different patterns of changes in viremia and T-cell markers. A statistically significant positive dose-response relationship was observed between inoculum titre and i) viremia trajectory-groups (r = 0.80, p<0.01), ii) CD8βlowCD62Lneg cell-fraction trajectory-groups (r = 0.56, p<0.01). Significant correlations were also found between viremia and the CD4/CD8 ratio and between seven out of ten T-cell markers.ConclusionsIn cats, the infectious dose determines early kinetics of viremia and initial CD8+ T-cell activation. An expansion of the CD8βlowCD62Lneg T-cells might be an early predictor of progression toward disease. The same might be expected in humans but needs confirmation.

Microsphere immunoassay for the detection of cytokines in domestic cat (Felis catus) plasma: Elevated IL-12/23 in acute feline immunodeficiency virus infections

We recently described the development and validation of a highly sensitive and specific microsphere immunoassay capable of simultaneously quantifying three domestic cat cytokines in tissue culture supernatant. Here we describe the modification of this assay to measure interferon gamma (IFNγ), interleukin (IL)-10 and IL-12/IL-23 p40 (IL-12/23) in domestic cat plasma, report values obtained from plasma collected after feline immunodeficiency virus (FIV) exposure, and compare plasma concentrations to blood cell mRNA expression. The validated quantitation limits of this assay are 31–1000pg/ml for IFNγ, 63–2000pg/ml for IL-10, and 20–625pg/ml for IL-12/23. Plasma cytokine levels from domestic cats infected with pathogenic and/or apathogenic FIV were determined at 3–4 and 7–8weeks post-infection. IL-12/23 was elevated (p<0.05) during acute infection with both FIV strains in two similar studies, conducted five years apart in different feline cohorts (n=44 total animals). IL-12/23 concentrations ranged from 377 to 1904pg/ml in naïve cats and 552 to 3460pg/ml in infected cats. In contrast, the majority of plasma samples had IFNγ and IL-10 concentrations below the lowest standard tested. The inability to consistently detect levels of IFNγ and IL-10 in plasma, despite the fact that mRNA changes were detected, suggests that these cytokines may be secreted and/or cleared in a more highly regulated manner than IL-12/23, or perhaps exert local effects under tighter peripheral constraints and/or at a lower effective concentration.

Feline tetherin (BST-2) restricts feline immunodeficiency virus release but not spreading infection

Background Tetherin (BST-2) is an interferon-inducible transmembrane protein that inhibits the release of enveloped viruses from infected cells. Here, we characterise the feline homologue of tetherin and assess its effects on the replication of feline immunodeficiency virus (FIV). Results A feline homologue of tetherin was amplified from IL2dependent T cell cDNA. Real-time PCR analyses revealed that feline tetherin transcripts were expressed in many feline cell lines and were induced by interferons (a, ω or g). Like human tetherin, feline tetherin displayed potent inhibition of FIV and HIV-1 particle release, however, this activity resisted antagonism by either HIV-1 VPU, or the FIV Env and “OrfA” proteins. Further, as over-expression of a complete FIV genome in trans could not overcome feline tetherin, these data suggest that FIV lacks a functional tetherin antagonist. When expressed stably in feline cell lines, tetherin did not abrogate the replication of FIV, indeed, syncytia formation was significantly enhanced in tetherin-expressing cells infected with CD134-independent strains of FIV (FIV Fca-F14 and FIV Pco-CoLV). Confocal microscopy revealed co-localisation of tetherin and FIV envelope glycoprotein (Env) in regions at the periphery of syncytia. Moreover, while treatment of feline cells with interferon-ω suppressed viral protein production and release (consistent with the pleiotropic actions of type-l interferon on viral replication), syncytia formation was enhanced in cells treated with interferon-ω either preor post- infection with a CD134-independent strain of FIV. Conclusions While feline tetherin prevents the release of nascent viral particles, cell to cell spread remains efficient in the presence of abundant viral receptors and interferoninduced up-regulation of tetherin expression may enhance syncytia formation. Accordingly, tetherin expression in vivo may promote the selective expansion of viral variants capable of more efficient cell to cell spread; contributing to the emergence of CD134-independent strains of FIV.

Viral transcriptome analysis of feline immunodeficiency virus infected cells using second generation sequencing technology

Feline immunodeficiency virus (FIV) is a widespread pathogen causing immunodeficiency in domestic cats and related wild cat species. The virus genome includes the main structural genes common to all retroviruses as well as accessory genes displaying essential functions during the viral life cycle. Expression of viral genes involves transcription of provirus genomes into full-length transcripts, which are partially processed into several spliced mRNA variants for the translation of particular proteins. Among several FIV isolates derived from domestic cats, notable differences in pathogenicity could be observed leading to identification of low and high pathogenic virus isolates. This study investigates the viral transcriptome of two differentially virulent FIV strains using second generation sequencing (SGS) technology. The expression levels of viral genes as detected by SGS were additionally determined by reverse transcription quantitative PCR analysis in order to compare two methods of mRNA quantification. The different properties of both methods, especially regarding normalization between samples, had to be considered when comparing the resulting data. SGS turned out to be a suitable technique for comparing mRNA transcription between both FIV infected cell lines and the identification of spliced viral transcripts. In contrast to this, the quantification of these spliced isoforms using SGS data was impeded by the short length of sequencing reads. In summary, SGS analysis revealed very consistent mRNA levels for the majority of viral genes between the low pathogenic Petaluma and the more highly pathogenic Glasgow 8 isolate. Notable differences among the two FIV strains could be observed in the viral mRNA splicing where Glasgow 8 displays similarities to the transcription pattern seen in the early stages of natural lentivirus infections. Thus, divergences in the regulation of post-transcriptional RNA processing might represent an additional contributor to the diverse pathogenic effects of individual FIV isolates. Taken together, this study aims to investigate the viral transcriptome as one part of the complex network of virus–host interactions, which will contribute to gaining deeper insights into FIV pathogenesis.

Strain-specific viral distribution and neuropathology of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV PPR (PPR, relatively apathogenic but associated with neurologic manifestations), FIV C36 (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3′ C36 genomic elements contribute to viral replication characteristics, and (ii) 5′ PPR genomic elements contribute to CNS manifestations. This study illustrates the potential for FIV to provide valuable information about neuroAIDS pathogenesis related to genotype and viral kinetics, as well as to identify strains useful to evaluation of therapeutic intervention.

The role of BST2/tetherin in feline retrovirus infection

Pathogenic retroviral infections of mammals have induced the evolution of cellular anti-viral restriction factors and have shaped their biological activities. This intrinsic immunity plays an important role in controlling viral replication and imposes a barrier to viral cross-species transmission. Well-studied examples of such host restriction factors are TRIM5α, an E3 ubiquitin ligase that binds incoming retroviral capsids in the cytoplasm via its C-terminal PRY/SPRY (B30.2) domain and targets them for proteasomal degradation, and APOBEC3 proteins, cytidine deaminases that induce hypermutation and impair viral reverse transcription. Tetherin (BST-2, CD317) is an interferon-inducible transmembrane protein that potently inhibits the release of nascent retrovirus particles in single-cycle replication assays. However, whether the primary biological activity of tetherin in vivo is that of a restriction factor remains uncertain as recent studies on human tetherin suggest that it is unable to prevent spreading infection of human immunodeficiency virus type 1 (HIV-1). The feline tetherin homologue resembles human tetherin in amino acid sequence, protein topology and anti-viral activity. Transiently expressed feline tetherin displays potent inhibition of feline immunodeficiency virus (FIV) and HIV-1 particle release. However, stable ectopic expression of feline tetherin in a range of feline cell lines has no inhibitory effect on the growth of either primary or cell culture-adapted strains of FIV. By comparing and contrasting the activities of the felid and primate tetherins against their respective immunodeficiency-causing lentiviruses we may gain insight into the contribution of tetherins to the control of lentiviral replication and the evolution of lentiviral virulence.

FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions

Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV Fca ) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV Ple ) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV Ple subtypes, the data suggest that FIV Ple subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations.

Phylogenetic characterisation of naturally occurring feline immunodeficiency virus in the United Kingdom

Feline immunodeficiency virus (FIV) is a significant pathogen of domestic and non-domestic felids worldwide. In domestic cats, FIV is classified into five distinct subtypes (A–E) with subtypes A and B distributed most widely. However, little is known about the degree of intrasubtype viral diversity and this may prove critical in determining whether monovalent vaccines are likely to protect against FIV strains within a single subtype. Here, we characterise novel env sequences from 47 FIV strains recovered from infected cats in the United Kingdom and its environs. Phylogenetic analyses revealed that all bar one sequence belonged to subtype A, the predominant subtype in Western Europe. A single sequence was identified as a likely subtype A/C recombinant, intriguing given that subtype C does not appear to exist in either the UK or North Western Europe and suggestive of a recombination event predating its introduction into the UK. Subtype A strains from the UK were not significantly differentiated from representative subtype A isolates found elsewhere suggesting multiple introductions of FIV into the country. Divergence among isolates was comparable to that observed for subtype A isolates worldwide, indicating that FIV in the UK covers the full spectrum of subtype A diversity seen globally. This study demonstrates that while subtype A is predominant in the UK, novel introductions may result in the emergence of novel subtypes or intersubtype recombinants, potentially circumventing vaccine strategies. However, the dominance of subtype A suggests that the development of a regional or subtype-specific protective vaccine for the UK could be achievable.

Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection

CD4 decline is a hallmark of disease onset in individuals infected with Feline Immunodeficiency Virus (FIV) or Human Immunodeficiency Virus type 1 (HIV-1). Cats that are infected with a poorly replicating, apathogenic FIV (PLV) prior to exposure to a virulent FIV strain (FIVC) maintain CD4 numbers by mechanisms that are not correlated with a measurable adaptive immune response or reduction in circulating viral load. We employed population genetic approaches based on the 3′ portion of the viral genome to estimate the population structure of FIVC from single and dual infected cats. In dual infected cats, FIVC effective population size was decreased during the initial viral expansion phase, and after three weeks of infection, the population declined sharply. The FIVC population recovered to pre-bottleneck levels approximately seven weeks post-FIVC infection. However, the population emerging from the bottleneck in dual infected cats was distinct based on estimates of temporal population structure and substitution profiles. The transition to transversion rate ratio (κ) increased from early to late phases in dual infected cats due primarily to a decrease in transversions whereas in single infected cats, κ declined over time. Although one clone with extensive G to A substitutions, indicative of host cytidine deaminase editing, was recovered from a dual infected cat during the bottleneck, the post bottleneck population had an overall reduction in G to A substitutions. These data are consistent with a model of PLV-induced host restriction, putatively involving host DNA editing, that alters the dynamics of FIVC throughout the course of infection leading to disease attenuation.