Feline Immunodeficiency Virus Research Articles

First Seroprevalence Study of Feline Leukemia and Feline Immunodeficiency Infections Among Cats in Algiers (Algeria) and Associated Risk Factors

Feline leukemia and feline immunodeficiency virus infections are two widespread diseases that affect the health of domestic cats all over the world. In Algeria, despite the existence of a large population of cats, there are no published data regarding the epidemiological status of feline retroviruses. Therefore, the objective of the present study was to estimate the seroprevalence of FIV and FeLV infections in cats in Algiers and to assess the main factors associated with the infection. A cross-sectional study was conducted in which 71 cats were sampled from several private veterinary clinics, and their obtained sera were tested using an immunochromatography analysis (SNAP Duo FIV/FeLV Test; Virbac Laboratories, France). The seroprevalence was about 32.39% and 22.53% for FIV and FeLV, respectively. Overall, 11.26% were positive for both infections. The present study showed that FIV seropositivity was associated with a younger age and health status (p < 0.05), while FeLV seropositivity was associated with the sex, reproductive status, housing, age, and health status of the cats. This preliminary study, which utilized rapid tests, provides important initial data revealing a relatively high prevalence of retroviruses in cats in Algeria. The results underscore the urgent need for implementing both preventive and management measures to control the spread of these retrovirus diseases. However, to enhance the reliability of future findings, it is essential to expand the sample size and incorporate reference diagnostic methods.

Serological and molecular detection of Toxoplasma gondii in cats in Europe with evaluation of associated risk factors for pathogen contact/infection.

Toxoplasma gondii is an obligate intracellular coccidian pathogen, with domestic cats and other members of the Felidae family serving as its definitive hosts. The aim of the study was to identify risk factors for positive test results. A laboratory database was screened for T gondii PCR results from faecal samples and serology results (IgM, IgG) from serum/plasma taken from cats in Europe between January 2008 and December 2022. Logistic regression analysis was performed to identify risk factors associated with positive T gondii results, such as breed, age, sex, neuter status, regionality, seasonality, feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) status. Odds ratios (ORs) were calculated. A total of 45,523 cats were included: 14,500 (31.9%) tested positive by direct and/or indirect detection methods for T gondii (PCR: 126/7896 [1.6%], IgG: 14,148/37,882 [37.3%], IgM: 1539/37,882 [4.1%]). Age >5 years (IgG: OR 2.591, P <0.001; IgM: OR 1.954, P <0.001), European domestic shorthair cats/cross breeds (IgG: OR 3.848, P <0.001; IgM: OR 2.152, P <0.001), male sex (IgG: OR 1.134, P <0.001), neuter status in male (IgG: OR 0.536, P <0.001) and female cats (IgG: OR 0.577, P <0.001), FeLV antigen positivity (IgG: OR 1.358, P = 0.030) and FIV antibody positivity (IgG: OR 2.350, P <0.001; IgM: OR 2.650, P <0.001) significantly impacted the serological results. In PCR testing, neuter status had a significant impact in male (OR 2.455, P = 0.002) and female cats (OR 2.988, P <0.001). Serological and PCR results were significantly influenced by regionality for IgG (central: OR 1.454, P <0.001; north: OR 0.768, P <0.001; south: OR 0.526, P <0.001; east: OR 0.768, P <0.001; west: OR 0.709, P <0.001), IgM (central: OR 0.616, P <0.001; north: OR 1.456, P <0.001; south: OR 1.767, P <0.001; east: OR 1.456, P <0.001) and PCR testing (central: OR 0.460, P <0.001; north: OR 3.020, P = 0.002; east: OR 3.020, P = 0.002). Seasonality had a statistically significant impact on IgM (summer: OR 1.402, P <0.001; winter: OR 0.732, P <0.001) and PCR testing (autumn: OR 1.473, P = 0.038). Breed, age, sex, neuter status, seasonality and regionality significantly impacted serological results. Neuter status, seasonality and regionality significantly impacted the PCR results. Immunosuppression (FeLV/FIV) had a significant impact on serological results. PCR-positive cats shed oocysts and spread infection to other susceptible hosts, including humans. Surveillance is therefore recommended, taking into consideration the associated risk factors.

The life cycle of feline immunodeficiency virus

The life cycle of feline immunodeficiency virus

Feline Vector-Borne Diseases and Their Possible Association with Hematological Abnormalities in Cats from Midwestern Brazil

Among the parasitic and infectious diseases affecting cats, those caused by vector-borne pathogens deserve attention due to their ability to cause nonspecific clinical signs and clinicopathological abnormalities. We studied the presence of Cytauxzoon spp., Ehrlichia spp., and Mycoplasma spp. in blood samples from 135 cats referred to the veterinary teaching hospital of the Federal University of Goiás in midwestern Brazil. We also investigated co-infections with Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) as well as the correlation between Mycoplasma spp. infection and cat variables, including age, sex, breed, and complete blood count abnormalities. Upon PCR testing, 20.7% (28/135) of samples were positive for Mycoplasma spp., 1.5% (2/135) for Cytauxzoon spp., and none for Ehrlichia spp. Co-infections with Mycoplasma spp. and Cytauxzoon spp. were detected in the two cats with the latter infection. Mycoplasma spp. infection was statistically associated with the simultaneous presence of thrombocytopenia and leukocytosis. This study confirms a high frequence of Mycoplasma spp. infection, with both M. haemofelis and ‘Candidatus Mycoplasma haemominutum’ circulating in this cat population. The clinical significance of Mycoplasma spp. infection in cats should be further explored and this infection should eventually be included in the differential diagnosis of thrombocytopenia and leukocytosis in otherwise apparently healthy cats.

DOENÇAS VIRAIS EM FELINOS SELVAGENS NATIVOS DO BRASIL

The aim of this study was to highlight the viral diseases affecting Brazil's native wild cats through a literature review of articles published between 1994 and 2023. Among the main viruses identified are feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), distemper virus (CDV), adenoviruses and rabies virus, among others. Some of these diseases are detected with significant frequency. Adenoviruses, on the other hand, have only been reported in one case involving wild cats in Brazil and are not a problem today; however, this occurrence is enough to consider them a potential future threat. Since viral agents have different incidences, symptoms and transmission behaviors, they should be studied taking their particularities into account. The degradation of nature by human actions and the interaction of these cats with domestic animals are factors that increase the risk of outbreaks. Understanding the incidence and cause of these diseases is essential for developing management and conservation strategies.

A Histopathological Study on the Changes in the Central Nervous System of Dead Cats With Neurological Symptoms

Background: Neurological conditions constitute approximately 10% of feline cases referred to veterinary clinics. Such cases often present manifestations of central nervous system (CNS) damage, including inflammatory lesions, neoplastic growth and structural and cellular transformations. Objectives: This study aimed at identifying histopathological changes in the CNS of cats that had succumbed to neurological symptoms. Methods: Microscopic evaluation of different sections within the CNS was conducted on 20 cats that had either died naturally or were euthanized due to neurological signs. After performing a necropsy, we examined the CNS tissues and conducted PCR testing to screen for possible viral infections, including feline infectious peritonitis (FIP), feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). Results: The majority of cases showed characteristic histopathologic lesions, notably mononuclear and suppurative meningoencephalitis, perivascular cuffing, disseminated intravascular coagulation (DIC), granulomatous meningoencephalitis, acute neuronal necrosis, liquefactive necrosis, epididymitis, thrombosis and demyelination. Among the 20 cats studied, 12 tested positive for FIP by PCR analysis, while 5 cats exhibited positive results for FIV. Also, FeLV PCR tests displayed positive results in 4 cats. No evidence of feline spongiform encephalopathy (FSE) was observed. Conclusion: This study is the first of its kind conducted in Iran. Based on the results, the most prevalent viral agents infecting cats’ CNS were FIP, FIV and FeLV. The investigation revealed no evidence of FSE in cats with neurological signs.

Incidence of Chlamydia spp., FIV, FeLV in Free-Roaming Cats in Slovakia.

Free-roaming cats represent a potential reservoir of infectious diseases. The most common co-infections of free-roaming cats include mixed viral, bacterial, fungal, yeast and parasitic infections. This study focuses on the occurrence of Chlamydia spp. feline immunodeficiency virus (FIV), feline leukaemia virus (FeLV) and their co-infections. The diseases accompanied by immune suppression, such as FIV, create favourable conditions for the onset of other diseases and co-infections. The result of co-infection may be a higher susceptibility for other pathogens, as well as the occurrence of more severe clinical symptoms. The study involved 168 (113♀ and 55♂) free-roaming adult cats during the years 2021-2022. All cats belonged to Slovak citizens with permanent residence in the Slovak Republic. Blood samples and swabs (Invasive EUROTUBO® Collection sterile swab, Deltalab O8191 Rubí, Spain) from the conjunctival sac were taken from 168 cats to be later tested by PCR and ELISA methods. Statistical analysis was also performed. The overall prevalence of Chlamydia spp. was 17.26%, of FIV 15.48%, and 5.95% of FeLV. The most significant finding in our study was 3.57% co-infection of FIV and Chlamydia spp. in tested cats. The observed prevalence of Chlamydia spp. FIV and FeLV indicates that the presence of these pathogens in populations of free-roaming cats is endemic.

Feline leishmaniosis in the Mediterranean Basin: a multicenter study

BackgroundCats are now recognized as competent hosts for Leishmania infantum and a blood source for sand fly vectors. Although canine leishmaniosis (CanL) is endemic in Mediterranean Basin countries, large-scale epidemiological studies are lacking for feline leishmaniosis (FeL). This study aimed to assess the prevalence of L. infantum infections, associated risk factors, clinical signs, and clinicopathological abnormalities in domestic cat populations from six Mediterranean Basin countries.MethodsFrom 2019 to 2022, blood and serum samples of cats (n = 2067) living in Italy (n = 300), Greece (n = 297), Portugal (n = 295), France (n = 231), Israel (n = 313), and Spain (n = 631) were collected along with animal data (i.e., age, sex, breed, housing conditions, and geographical origin), clinical signs, and laboratory blood test parameters. Cats were grouped according to their age as kittens (up to 1 year), young (older than 1 and younger than 7 years), mature (between 7 and 10 years), and senior (older than 10 years). Serum samples were tested for L. infantum by immunofluorescence antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA), and blood samples of seropositive cats were tested for L. infantum kinetoplast deoxyribonucleic acid (kDNA). Viral infection by feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) was molecularly addressed in all cats enrolled. Statistical analysis was performed to evaluate the association between the risk of L. infantum infection and independent variables, and among co-infection of L. infantum with FIV and/or FeLV, clinical signs, and clinicopathological abnormalities.ResultsOverall, 17.3% (358/2067) of cats scored positive for L. infantum by serological tests. Specifically, 24.7% were from Portugal, 23.2% from Greece, 16.6% from Israel, 15% from Spain, 13.3% from France, and 12.6% from Italy. Leishmania infantum DNA was detected in 15 seropositive animals. Housing condition and FIV infection proved to be risk factors for FeL. Leishmania seropositivity was significantly associated with weight loss, lymphadenomegaly, gingivostomatitis, and oral ulcers, as well as with reduced albumin and albumin/globulin ratio, increased total globulins and total proteins, leukocytosis, and thrombocytosis.ConclusionsThis study provides, for the first time, a large-scale epidemiological survey on FeL and its clinical presentation, revealing that L. infantum circulates among domestic cats, especially shelter/free-roaming and FIV-infected animals, living in CanL endemic countries of the Mediterranean Basin.Graphical

Global seroprevalence and factors associated with seropositivity for feline immunodeficiency virus (FIV) in cats: A systematic review and meta-analysis

The feline immunodeficiency virus (FIV) is a retrovirus of the Lentivirus genus, distributed worldwide, that causes persistent infection with a significant impact on the cats’ health. Due to the importance of this infection in feline medicine, this pioneering study aimed to obtain an integrated estimate of the global seroprevalence of FIV in cats and to characterize the factors associated with this infection. Four electronic databases were screened for observational studies with FIV seroprevalence in cats published globally for this systematic review and meta-analysis. The initial search method returned 873 studies, of which 113 met all predefined criteria and were therefore included in this review. Meta-analysis with general data was performed, and a combined global seropositivity of 9.43 % (95 % CI: 8.24 % – 10.78 %) was found. Seropositivity was 14.34 % (95 % CI = 10.92 % – 18.61 %) in Asia, 11.90 % (95 % CI = 9.82 % – 14.34 %) in Oceania, 10.90 % (95 % CI = 5.71 % – 19.82 %) in Central America, 9.43 % (95 % CI = 6.95 % – 12.66 %) in South America, 9 % (95 % CI = 0 – 80 %) in Africa, 8.98 % (95 % CI = 7.31 % – 10.98 %) in Europe, and 5.93 % (95 % CI = 4.33 % – 8.07 %) in North America. Meta-analysis of factors associated with seropositivity demonstrated that FIV seroprevalence was higher in male (Prevalence ratio [PR] = 2.53, 95 % CI = 2.16 – 2.95), adult (PR = 2.83, 95 % CI = 2.24 – 3.56), unowned status (PR = 1.47, 95 % CI = 1.07 – 2.03), sick status (PR = 2.46, 95 % CI = 1.97 – 3.06), and cats with outdoor access (PR = 4.38, 95 % CI = 2.26 – 8.47). The results demonstrated that FIV is globally distributed and has a high seroprevalence in some geographical areas. Information compiled from this research is relevant to understanding the worldwide epidemiology of FIV. It presents the potential to contribute to the planning of strategies focused on controlling and reducing cases in cat populations.

The erythrocyte sedimentation rate and other markers of inflammation in cats tested for Leishmania infantum and feline immunodeficiency virus antibodies

BackgroundIn endemic areas, Leishmania infantum and feline immunodeficiency virus (FIV) co-infection occurs in cats, and may favour a progressive course of feline leishmaniosis. Abnormalities in serum protein fractions have been reported, but inflammation markers have scarcely been studied. Erythrocyte sediment rate (ESR) is a marker of inflammation that is poorly used in veterinary medicine, but it has been evaluated in EDTA blood using a recently introduced automatic device. We studied ESR and a pool of feline markers of inflammation (MoI) in cats L. infantum (Li+) and/or FIV antibody-positive (Li+FIV+/FIV+) with the aims (a) to evaluate ESR as MoI in cats with the infectious and clinical conditions considered and (b) to provide data about a pool of MoI never investigated in the feline infections studied and in other cat diseases before.MethodsThis prospective controlled study included 35 study group cats (Li+, n = 20; FIV +, n = 8; Li+FIV+, n = 7) and ten healthy antibody-negative control cats. Clinical findings at physical examination and selected clinical pathological abnormalities related to inflammation were statistically analysed in relation to the infectious status and ESR values.ResultsESR values were higher in Li+, FIV+, and Li+FIV+ cats compared with control cats, and 40% of the study group cats had ESR values above the reference interval (RI). ESR positively correlated with some positive MoI and negatively with some negative MoI studied. Additionally, a higher prevalence of ESR values above the RI has been detected in cats with hypoalbuminemia or hypergammaglobulinemia and higher ESR values were measured in cats with serum protein electrophoresis (SPE) fraction abnormalities. Correlations were also found with erythrocytes, hemoglobin, hematocrit and some erythrocyte indices. FIV+ and Li+FIV+ cats had a higher prevalence of increased ESR values, and almost all had SPE abnormalities and more severe clinical presentations compared with Li+ cats.ConclusionsAbnormal levels of MoI were found in almost all parameters studied, particularly in FIV+ and Li+FIV+ cats. Also, ESR can be used as a marker of inflammation in cats with L. infantum and/or FIV infection.Graphical

Primary immune‐mediated neutropenia and precursor‐targeted immune‐mediated anaemia in a 4‐year‐old cat

AbstractA 4‐year‐old, female, neutered, domestic shorthair was presented for acute onset of lethargy. The cat had been diagnosed with and treated for precursor‐targeted immune‐mediated anaemia 2 years before presentation. The clinical examination was unremarkable. Haematology and biochemistry revealed neutropenia and hyperglobulinaemia. Electrophoresis revealed polyclonal gammopathy. Toxoplasma spp. IgG/IgM, Bartonella spp., feline immunodeficiency virus and feline leukaemia virus serology were negative. Urine culture was negative. A computed tomography scan of the thorax and abdomen revealed an enlarged spleen, and cytology was suggestive of reactive lymphoid hyperplasia. Bone marrow aspirates and biopsies were supportive of primary immune‐mediated neutropenia and recurrence of precursor‐targeted immune‐mediated anaemia. The cat was treated successfully with prednisolone and cyclosporine. The necessity to perform a bone marrow biopsy should be highlighted in this case, as the diagnosis of precursor‐targeted immune‐mediated anaemia and immune‐mediated neutropenia was based on bone marrow sampling, exclusion of infectious disorders and response to immunosuppressive medications.

Conformational analysis of a new peptide derived from feline immunodeficiency virus gp36 in SDS micelles: An NMR-MD based investigation.

Feline immunodeficiency virus (FIV) shares structural similarities with human immunodeficiency virus (HIV): the surface glycoprotein gp36 corresponds to the HIV gp41, which drives virus-host cell interactions and is targeted by the peptide entry inhibitor enfuvirtide. Following a similar drug design strategy for the development of an anti-FIV therapy, the present study investigates 627-646gp36 NHR, a peptide sequence derived from a region of gp36 that was previously found to interfere with the antiviral activity of the peptide C8, which instead derives from the gp36 MPER. CD, NMR, and MD simulations were employed to probe the conformational characteristics of 627-646gp36 NHR in the membrane-mimicking environment of SDS micelles. Our data show that 627-646gp36 NHR is characterized by three dynamic helix structures. MD simulations involving 627-646gp36 NHR, C8, and a larger protein, including the CHR and MPER regions, suggest that the interaction of C8 with the MPER region, the origin of the antiviral activity of C8, is disfavored in the presence of 627-646gp36 NHR in the simulation. This evidence can be useful for interpreting the molecular mechanism that leads to interference with the activity of C8, providing information on the folding/unfolding mechanism of the viral glycoprotein to design new strategies to inhibit viral entry.

Impacts of Antiretroviral Therapy on the Oral Microbiome and Periodontal Health of Feline Immunodeficiency Virus Positive Cats.

Feline immunodeficiency virus (FIV) is the domestic cat analogue of HIV infection in humans. Both viruses induce oral disease in untreated individuals, with clinical signs that include gingivitis and periodontal lesions. Oral disease manifestations in HIV patients are abated by highly effective combination antiretroviral therapy (cART), though certain oral manifestations persist despite therapy. Microorganisms associated with oral cavity opportunistic infections in patients with HIV cause similar pathologies in cats. To further develop this model, we evaluated characteristics of feline oral health and oral microbiome during experimental FIV infection over an 8-month period following cART. Using 16S metagenomics sequencing, we evaluated gingival bacterial communities at four timepoints in uninfected and FIV-infected cats treated with cART or placebo. Comprehensive oral examinations were also conducted by a veterinary dental specialist over the experimental period. Gingival inflammation was higher in FIV-infected cats treated with placebo compared to cART-treated cats and controls at study endpoint. Oral microbiome alpha diversity increased in all groups, while beta diversity differed among treatment groups, documenting a significant effect of cART therapy on microbiome community composition. This finding has not previously been reported and indicates cART ameliorates immunodeficiency virus-associated oral disease via preservation of oral mucosal microbiota. Further, this study illustrates the value of the FIV animal model for investigations of mechanistic associations and therapeutic interventions for HIV oral manifestations.

Antimicrobial use practices in canine and feline patients with co-morbidities undergoing dental procedures in primary care practices in the US.

This study aimed to investigate how the presence of co-morbid conditions influenced antimicrobial usage as presumptive prophylaxis for suspected bacteremia in dogs and cats undergoing dental treatments at primary care veterinary clinics in the United States. In 2020, data was collected from 1076 veterinary clinics across 44 US states. A total of 681,541 general anesthesia dental procedures were conducted on 592,472 dogs and 89,069 cats. This revealed that systemic antimicrobials were administered in 8.8% of dog procedures and 7.8% of cat procedures in the absence of concurrent periodontal disease or extractions. Cefpodoxime, clindamycin, and amoxicillin-clavulanate were the most frequently used antimicrobials in dogs, while cefovecin, amoxicillin-clavulanate, and clindamycin topped the list for cats. Dogs with cardiovascular, hepato-renal, and endocrine co-morbidities, as well as those undergoing concurrent removal of cutaneous or subcutaneous neoplasia, displayed higher antimicrobial use. Similarly, cats with endocrine or hepato-renal disease, retroviral infection (i.e., feline leukemia virus (FeLV), feline immunodeficiency virus (FIV)), and concurrent removal of cutaneous or subcutaneous neoplasia exhibited increased antimicrobial use. Dogs with hepato-renal abnormalities had longer treatment durations compared to those without (10.1 vs. 9.6 days). Conversely, cats with concurrent removal of cutaneous or subcutaneous neoplasia had shorter durations of treatment as compared to those that did not have this procedure performed (8.4 vs 9.2 days). The findings of this study underscore the necessity for further research and collaboration within the veterinary community to develop evidence-based guidelines, promoting responsible antimicrobial use, and advancing the field of veterinary dentistry for enhanced patient outcomes.

Study of feline immunodeficiency virus prevalence and expert opinions on standards of care.

The purpose of this study was to identify knowledge gaps in the global prevalence of feline immunodeficiency virus (FIV) and to obtain professional opinions and experiences regarding FIV in selected countries. We conducted a literature review of abstracts that reported the prevalence of FIV and interviewed experts in feline medicine and retroviruses from different countries to determine regional perspectives. A total of 90 articles reporting FIV prevalence as a primary unbiased population-level analysis between 1980 and 2017 were indexed. FIV prevalence, demographics, year and location were analyzed. Statistics were evaluated and compared. In total, 10 experts were interviewed. Results were analyzed for congruence with the findings of the literature review. FIV prevalence was typically in the range of 5-8%, with a global prevalence of 4.7%, and remained largely constant over the reporting period (1980-2017). Over 90% of articles reported greater prevalence in older male cats. More studies were conducted in North America and Europe and reported the lowest prevalence. Expert-estimated prevalence approximated literature review prevalence. Attitudes and recommendations for management were consistent among experts. The limitations of the present review include varying inclusion criteria of cats tested in different studies, variation in testing modalities and the inability to conduct summary statistics across dissimilar cohorts. The global prevalence of FIV has not changed since its discovery 40 years ago. Prevalence is higher in older male cats and is lower in North America and Europe than other continents. Experts agree that FIV is not typically a disease of high concern and is often associated with infections of the oral cavity. Vaccination is not typically recommended and has been discontinued in North America. The evaluation of risk factors for FIV progression is useful in managing infections. Recommendations for future research include analyses to determine copathogen and environmental factors that impact progression, assessment of life span impacts and investigations of treatment efficacy and side effects.

The assembly-defective phenotype of an FIV Gag polyprotein containing the SIV nucleocapsid zinc finger motifs is reversed by including the SIV SP2 domain in the chimeric protein

To gain insight into the functional relationship between the nucleocapsid (NC) domains of the Gag polyproteins of feline and simian immunodeficiency viruses, FIV and SIV, respectively, we generated two FIV Gag chimeric proteins containing different SIV NC and gag sequences. A chimeric FIV Gag protein (NC1) containing the SIV two zinc fingers motifs was incapable of assembling into virus-like particles. By contrast, another Gag chimera (NC2) differing from NC1 by the replacement of the C-terminal region of the FIV NC with SIV SP2 produced particles as efficiently as wild-type FIV Gag. Of note, when the chimeric NC2 Gag polyprotein was expressed in the context of the proviral DNA in feline CrFK cells, wild-type levels of virions were produced which encapsidated 50% of genomic RNA when compared to the wild-type virus.

Utilizing Feline Lentiviral Infection to Establish a Translational Model for COVID-19 in People with Human Immunodeficiency Virus Infection.

People living with human immunodeficiency virus (PLWH) are a significant population globally. Research delineating our understanding of coinfections in PLWH is critical to care for those navigating infection with other pathogens. The recent COVID-19 pandemic underscored the urgent need for studying the effects of SARS-CoV-2 infections in therapy-controlled and uncontrolled immunodeficiency viral infections. This study established the utility of a feline model for the in vivo study of coinfections. Domestic cats are naturally infected with SARS-CoV-2 and Feline Immunodeficiency Virus, a lentivirus molecularly and pathogenically similar to HIV. In this study, comparisons are made between FIV-positive and FIV-negative cats inoculated with SARS-CoV-2 (B.1.617.2.) in an experimental setting. Of the FIV+ cats, three received Zidovudine (AZT) therapy in the weeks leading up to SARS-CoV-2 inoculation, and two did not. SARS-CoV-2 viral RNA was quantified, histopathologic comparisons of respiratory tissues were made, and T-cell populations were analyzed for immune phenotype shifts between groups. CD4+ T lymphocyte responses varied, with FIV+-untreated cats having the poorest CD4+ response to SARS-CoV-2 infection. While all cats had significant pulmonary inflammation, key histopathologic features of the disease differed between groups. Additionally, viral genomic analysis was performed, and results were analyzed for the presence of emerging, absent, amplified, or reduced mutations in SARS-CoV-2 viral RNA after passage through the feline model. Positive selection is noted, especially in FIV+ cats untreated with AZT, and mutations with potential relevance were identified; one FIV+-untreated cat had persistent, increasing SARS-CoV-2 RNA in plasma five days post-infection. These findings and others support the utility of the feline model for studying coinfection in people with HIV and highlight the importance of antiretroviral therapy in clearing SARS-CoV-2 coinfections to minimize transmission and emergence of mutations that may have deleterious effects.

Molecular Detection and Genetic Characterization of Feline Immunodeficiency Virus (FIV) in Seropositive Cats in Northern Italy.

Feline immunodeficiency virus (FIV) is responsible for immunodeficiency syndrome in cats. Several viral subtypes have been identified, each with a variable geographical distribution. To date, the subtype B is known to be the genotype spread in Italy. In this study, the genetic diversity of FIV in northern Italy was assessed by detecting proviral DNA in the blood samples of 50 cats determined to be positive through an anti-FIV antibodies test. These cats were tested using six different PCR assays, and the identified viruses were sequenced and analyzed. Forty-eight cats were confirmed positive, and several FIV subtypes were characterized. As expected, the subtype B was the most commonly observed, and the subtype A was reported for the first time in Italy. Moreover, a new taxon possibly representing an additional FIV subtype was detected, and one virus belonging to subtype B potentially had a recombinant origin. The genetic variability between the FIV viruses that emerged in this study may lead to the potential diagnostic failure of single molecular tests. Therefore, a new diagnostic strategy, which adopts different molecular tests and sequencing, is recommended to monitor the evolution and spread of FIV.

Evaluation of leukocyte ratios as survival prognostic markers in feline retrovirus infections

The utility of neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) as prognostic markers in Feline Leukemia Virus (FeLV) and Feline Immunodeficiency Virus (FIV) infections has not yet been investigated. The aim of this study was to investigate these leukocyte ratios in retrovirus-positive cats and to evaluate their prognostic value for survival. This retrospective case-control study included 142 cats, 75 FIV-Antibodies (Ab)-positive, 52 FeLV-Antigen (Ag)-positive, and 15 FIV-Ab+FeLV-Ag-positive, and a control population of 142 retrovirus-negative age-, sex-, and lifestyle-matched cats. Signalment, complete blood count at the time of serological testing, and outcome were recorded. Leukocyte ratios were compared within the same case-control population, among the three retrovirus-seropositive populations, and were related to survival time. No significant difference was found in NLR, MLR, or PLR between FIV-Ab-positive and FIV-Ab+FeLV-Ag-positive cats and their cross-matched controls. In the FeLV-Ag-positive population, MLR was significantly lower than in the control population (0.05 and 0.14, respectively, P=0.0008). No ratio discriminated among the three infectious states. No ratio was significantly different between survivors and non-survivors in the population of FIV-Ab-positive cats. MLR at diagnosis was significantly higher in FeLV-Ag-positive cats that died 1–3 years after diagnosis than in FeLV-Ag-positive cats still alive at 3 years (P=0.0284). None of the three ratios could predict retroviruses-positive cats that would survive to the end of the study. Overall the results indicate that NLR, MLR, and PLR are not significantly different among retrovirus statuses evaluated and had a very limited prognostic value for the survival time in retrovirus-positive cats.

Comparison of feline and human immunodeficiency virus reverse transcriptase enzymes through chemical screening and computational analysis.

Feline immunodeficiency virus (FIV) is a common infection found in domesticated and wild cats worldwide. Despite the wealth of therapeutic understanding of the disease in humans, considerably less information exists regarding the treatment of the disease in felines. Current treatment relies on drugs developed for the related human immunodeficiency virus (HIV) and includes compounds of the popular non-nucleotide reverse transcriptase (NNRTI) class. This is despite FIV-RT being only 67% similar to HIV-1 RT at the enzyme level, increasing to 88% for the allosteric pocket targeted by NNRTIs. The goal of this project was to try to quantify how well the more extensive pharmacological knowledge available for human disease translates to felines. To this end we screened known NNRTIs and 10 diverse pyrimidine analogs identified virtually. We use this chemo-centric probe approach to (a) assess the similarity between the two related RT targets based on the observed experimental inhibition values, (b) try to identify more potent inhibitors at FIV, and (c) gain a better appreciation of the structure-activity relationships (SAR). We found the correlation between IC50s at the two targets to be strong (r2 = 0.87) and identified compound 1 as the most potent inhibitor of FIV with IC50 of 0.030 μM ± 0.009. This compared to FIV IC50 values of 0.22 ± 0.17 μM, 0.040 ± 0.010 μM and >160 μM for known anti HIV-1 RT drugs Efavirenz, Rilpivirine, and Nevirapine, respectively. This knowledge, along with an understanding of the structural origin that give rise to any differences could improve the way HIV drugs are repurposed for FIV.