Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus (FIV)

Analysing the evolution of FIV on the intra-host level is important, in order to address whether the diversity and composition of viral quasispecies affects disease progression.<p></p> We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at the rate of 1.16 x 10-3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3-V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3-V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation.<p></p> Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximal evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared to HIV might explain why many naturally infected cats do not progress to AIDS rapidly.<p></p&gt

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.<p></p> 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.<p></p&gt

Truncation of TRIM5 in the <i>Feliformia</i> explains the absence of retroviral restriction in cells of the domestic cat

TRIM5[alpha] mediates a potent retroviral restriction phenotype in diverse mammalian species. Here, we identify a TRIM5 transcript in cat cells with a truncated B30.2 capsid binding domain and ablated restrictive function which, remarkably, is conserved across the &lt;i&gt;Feliformia&lt;/i&gt;. Cat TRIM5 displayed no restriction activity, but ectopic expression conferred a dominant negative effect against human TRIM5[alpha]. Our findings explain the absence of retroviral restriction in cat cells and suggest that disruption of the TRIM5 locus has arisen independently at least twice in the &lt;i&gt;Carnivora&lt;/i&gt;, with implications concerning the evolution of the host and pathogen in this taxon

The comparative value of feline virology research: can findings from the feline lentiviral vaccine be translated to humans?

Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that shares several similarities with its human counterpart, human immunodeficiency virus (HIV). Their analogies include genomic organization, lymphocyte tropism, viral persistence and induction of immunodeficiency. FIV is the only lentivirus for which a commercial vaccine is registered for prevention in either human or veterinary medicine. This provides a unique opportunity to investigate the mechanisms of protection induced by lentivirus vaccines at the population level and might contribute to the development of efficacious HIV vaccines. As well as having comparative value for vaccine studies, FIV research has shed some light on the relationship between lentiviral tropism and pathogenesis. Recent studies in our laboratory demonstrated that the interaction between FIV and its primary receptor changes as disease progresses, reminiscent of the receptor switch observed as disease progresses in HIV infected individuals. Here we summarise findings illustrating that, in addition to its veterinary significance, FIV has comparative value, providing a useful model to explore lentivirus–host interactions and to examine potential immune correlates of protection against HIV infection

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

&lt;b&gt;Background&lt;/b&gt; Feline 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.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Findings&lt;/b&gt; Here, 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.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; These findings are consistent with a shift in CRD2 of CD134 usage with disease progression.&lt;p&gt;&lt;/p&gt

Duration of antibody response following vaccination against feline immunodeficiency virus

Objectives: Recently, two point-of-care (PoC) feline immunodeficiency virus (FIV) antibody test kits (Witness and Anigen Rapid) were reported as being able to differentiate FIV-vaccinated from FIV-infected cats at a single time point, irrespective of the gap between testing and last vaccination (0–7 years). The aim of the current study was to investigate systematically anti-FIV antibody production over time in response to the recommended primary FIV vaccination series. Methods: First, residual plasma from the original study was tested using a laboratory-based ELISA to determine whether negative results with PoC testing were due to reduced as opposed to absent antibodies to gp40. Second, a prospective study was performed using immunologically naive client-owned kittens and cats given a primary FIV vaccination series using a commercially available inactivated whole cell/inactivated whole virus vaccine (Fel-O-Vax FIV, three subcutaneous injections at 4 week intervals) and tested systematically (up to 11 times) over 6 months, using four commercially available PoC FIV antibody kits (SNAP FIV/FeLV Combo [detects antibodies to p15/p24], Witness FeLV/FIV [gp40], Anigen Rapid FIV/FeLV [p24/gp40] and VetScan FeLV/FIV Rapid [p24]). Results: The laboratory-based ELISA showed cats from the original study vaccinated within the previous 0–15 months had detectable levels of antibodies to gp40, despite testing negative with two kits that use gp40 as a capture antigen (Witness and Anigen Rapid kits). The prospective study showed that antibody testing with SNAP Combo and VetScan Rapid was positive in all cats 2 weeks after the second primary FIV vaccination, and remained positive for the duration of the study (12/12 and 10/12 cats positive, respectively). Antibody testing with Witness and Anigen Rapid was also positive in a high proportion of cats 2 weeks after the second primary FIV vaccination (8/12 and 7/12, respectively), but antibody levels declined below the level of detection in most cats (10/12) by 1 month after the third (final) primary FIV vaccination. All cats tested negative using Witness and Anigen Rapid 6 months after the third primary FIV vaccination. Conclusions and relevance: This study has shown that a primary course of FIV vaccination does not interfere with FIV antibody testing in cats using Witness and Anigen Rapid, provided primary vaccination has not occurred within the previous 6 months. Consequently, Witness and Anigen Rapid antibody test kits can be used reliably to determine FIV infection status at the time of annual booster FIV vaccination to help detect ‘vaccine breakthroughs’ and in cats that have not received a primary course of FIV vaccination within the preceding 6 months. The duration of antibody response following annual booster FIV vaccination and the resulting effect on antibody testing using PoC kits needs to be determined by further research. The mechanism(s) for the variation in FIV antibody test kit performance remains unclear

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Patient and carer experiences of pain care in an Australian regional comprehensive cancer care setting: a qualitative study.

INTRODUCTION: Pain is a common and distressing symptom in people living with cancer that requires a patient-centred approach to management. Since 2010, the Australian Government has invested heavily in developing regional cancer centres to improve cancer outcomes. This study explored patient and carer experiences of care from a regional cancer centre with specific reference to cancer pain management. METHODS: A qualitative approach was used with semi-structured telephone interviews. Participants were outpatients at a regional cancer centre in New South Wales who had reported worst pain of 2 or more on a 0-10 numerical rating scale, and their carers. Questions explored experiences of pain assessment and management, and perceptions of how these were affected by the regional setting. Researchers analysed data using a deductive approach, using Mead and Bower's (2000) framework of factors influencing patient-centred care. RESULTS: Eighteen telephone interviews were conducted with 13 patients and 5 carers. Participants perceived that living in a regional setting conferred advantages to the patient-centredness of care via influences at the levels of professional context, the doctor-patient relationship, and consultation. These influences included established and ongoing relationships with a smaller number of care providers who were members of the community, and heightened accessibility in terms of travel/parking, flexible appointments, and ample time spent with each patient. The first of these factors was also perceived to contribute to continuity of care between specialist and primary care providers. However, one negative case reported disagreement between providers and a difficulty accessing specialist pain services. Several participants also reported a preference, and unmet need, for non-pharmacological rather than pharmacological pain management. CONCLUSION: While much research has focused on lack of services and poorer outcomes for people with cancer in rural areas, the Australian regional setting may offer benefits to the patient-centredness of cancer pain management and continuity of care. More research is needed to better understand the benefits and trade-offs of cancer care in regional versus urban settings, and how each can learn from the other. An unmet need for non-pharmacological rather than pharmacological pain management is among the most consistent findings of qualitative studies of patient/carer preferences across settings

Endometrial response to IVF hormonal manipulation: Comparative analysis of menopausal, down regulated and natural cycles

BACKGROUND: Uterine luminal epithelial cell response to different hormonal strategies was examined to determine commonality when an endometrium attains a receptive, stimulated, morphological profile that may lead to successful implantation. METHODS: Endometrial biopsies from 3 cohorts of patients were compared. The tissue samples taken from these patients were categorized into 8 different groups according to their baseline and the hormone regime used. RESULTS: Pre-treatment natural cycle tissue was variable in appearance. Downregulation with a GnRH analogue tissue appeared menopausal in character. HRT after downregulation resulted in tissue uniformity. HRT in menopause resulted in a 'lush' epithelial surface. HST in the natural cycle improved the morphology with significant difference in secretion between the two regimes examined. CONCLUSIONS: Down regulation plus HRT standardized surface appearance but tissue response is significantly different from the natural cycle, natural cycle plus HRT or menopause plus HRT. HRT in menopause reinstates tissue to a state similar to a natural cycle but significantly different from a natural cycle plus HST. HST with a natural cycle is similar to tissue from the natural cycle but significant differences reflect the influence of the particular hormones present (at any point) within the cycle