scholarly journals Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 805
Author(s):  
Craig Miller ◽  
Jordan Powers ◽  
Esther Musselman ◽  
Ryan Mackie ◽  
John Elder ◽  
...  

Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections.

2012 ◽  
Vol 279 (1745) ◽  
pp. 4206-4214 ◽  
Author(s):  
M. Maas ◽  
D. F. Keet ◽  
V. P. M. G. Rutten ◽  
J. A. P. Heesterbeek ◽  
M. Nielen

Bovine tuberculosis (BTB), caused by Mycobacterium bovis , is a disease that was introduced relatively recently into the Kruger National Park (KNP) lion population. Feline immunodeficiency virus (FIV ple ) is thought to have been endemic in lions for a much longer time. In humans, co-infection between Mycobacterium tuberculosis and human immunodeficiency virus increases disease burden. If BTB were to reach high levels of prevalence in lions, and if similar worsening effects would exist between FIV ple and BTB as for their human equivalents, this could pose a lion conservation problem. We collected data on lions in KNP from 1993 to 2008 for spatio-temporal analysis of both FIV ple and BTB, and to assess whether a similar relationship between the two diseases exists in lions. We found that BTB prevalence in the south was higher than in the north (72 versus 19% over the total study period) and increased over time in the northern part of the KNP (0–41%). No significant spatio-temporal differences were seen for FIV ple in the study period, in agreement with the presumed endemic state of the infection. Both infections affected haematology and blood chemistry values, FIV ple in a more pronounced way than BTB. The effect of co-infection on these values, however, was always less than additive. Though a large proportion (31%) of the lions was co-infected with FIV ple and M. bovis , there was no evidence for a synergistic relation as in their human counterparts. Whether this results from different immunopathogeneses remains to be determined.


Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 655 ◽  
Author(s):  
Junier ◽  
Huber ◽  
Schmutz ◽  
Kufner ◽  
Zagordi ◽  
...  

Shotgun metagenomics using next generation sequencing (NGS) is a promising technique to analyze both DNA and RNA microbial material from patient samples. Mostly used in a research setting, it is now increasingly being used in the clinical realm as well, notably to support diagnosis of viral infections, thereby calling for quality control and the implementation of ring trials (RT) to benchmark pipelines and ensure comparable results. The Swiss NGS clinical virology community therefore decided to conduct a RT in 2018, in order to benchmark current metagenomic workflows used at Swiss clinical virology laboratories, and thereby contribute to the definition of common best practices. The RT consisted of two parts (increments), in order to disentangle the variability arising from the experimental compared to the bioinformatics parts of the laboratory pipeline. In addition, the RT was also designed to assess the impact of databases compared to bioinformatics algorithms on the final results, by asking participants to perform the bioinformatics analysis with a common database, in addition to using their own in-house database. Five laboratories participated in the RT (seven pipelines were tested). We observed that the algorithms had a stronger impact on the overall performance than the choice of the reference database. Our results also suggest that differences in sample preparation can lead to significant differences in the performance, and that laboratories should aim for at least 5–10 Mio reads per sample and use depth of coverage in addition to other interpretation metrics such as the percent of coverage. Performance was generally lower when increasing the number of viruses per sample. The lessons learned from this pilot study will be useful for the development of larger-scale RTs to serve as regular quality control tests for laboratories performing NGS analyses of viruses in a clinical setting.


2019 ◽  
pp. 767-801
Author(s):  
Paul Grime ◽  
Christopher Conlon

Hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) infections have particular implications for fitness for work. These include the impact of symptoms and disease, the transmissibility of infection in the course of specific work activities, and, in the case of HIV, vulnerability to other infections arising from immune deficiency. This chapter focuses on HBV, HCV, and HIV because these are the most common blood-borne viruses that have particular implications for work. Blood-borne viral infections can affect people of any age. In the UK, HIV infection is specifically mentioned and automatically considered as a disability, from the point of diagnosis, by the Equality Act 2010. HBV and HCV infections may also qualify as disabilities, if associated disease causes impairment. There are therefore practical, legal, and ethical issues to consider when assessing fitness for work in people with blood-borne viral infections.


2020 ◽  
Vol 50 (12) ◽  
Author(s):  
Isadora Duarte Santos Frota ◽  
Jéssica de Oliveira Souza ◽  
Fernanda de Oliveira Busato ◽  
Cristina Abreu de Araujo ◽  
Flávio Curbani ◽  
...  

ABSTRACT: Feline leukemia virus (FeLV) causes an infection in cats that, in some cases, can also be reported with other pathologies, such as infection with feline immunodeficiency virus (FIV), feline infectious peritonitis (FIP), and lymphoma. Although, a compromised immune response is reported in these animals, little is known about the immunological state of their cells. To shed some light in this area, we studied peripheral blood samples from both infected and non-infected cats with FeLV, with or without FIV, FIP, and lymphoma. We tested a panel of monoclonal antibodies (n=11) against mouse and human antigens and we reported that cat leukocytes can be stained with anti-mouse B220 monoclonal antibody; therefore, percentages of B cells were evaluated in different cat groups. Our results showed that cats with FeLV and FIP, or with leukemia, presented a large decrease in B220+ mononuclear cells. However, FeLV+ cats without clinical signs, or with unspecific clinical signs, had the same amount of B220+ mononuclear cells as healthy cats (control cats). Since the expression of B220 is exclusively restricted to the naïve B cell population, we inferred that the absence of these B cells in FeLV+ cats is related to other conditions that affect B cell numbers, such as viral infections and leukemias. Therefore, the amount of naïve B cells in peripheral blood (i.e., B220+ cells) can be used to identify FeLV+ cats concomitantly carrying FIP or leukemia, from FeLV+ cats with lymphoma or without any clinical signs.


2010 ◽  
Vol 43 (6) ◽  
pp. 624-628 ◽  
Author(s):  
Natalia Saldanha Magalhães Coca ◽  
Marcelo Silva Oliveira ◽  
Izabela Voieta ◽  
Carlos Maurício de Figueiredo Antunes ◽  
José Roberto Lambertucci

INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls. METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the frequency of hepatotoxicity I was 77% and 46%, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4%) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I. CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.


2021 ◽  
Vol 61 (1) ◽  
pp. 565-585
Author(s):  
Zaikuan J. Yu ◽  
Eric P. Mosher ◽  
Namandjé N. Bumpus

Antiretroviral therapy has markedly reduced morbidity and mortality for persons living with human immunodeficiency virus (HIV). Individual tailoring of antiretroviral regimens has the potential to further improve the long-term management of HIV through the mitigation of treatment failure and drug-induced toxicities. While the mechanisms underlying anti-HIV drug adverse outcomes are multifactorial, the application of drug-specific pharmacogenomic knowledge is required in order to move toward the personalization of HIV therapy. Thus, detailed understanding of the metabolism and transport of antiretrovirals and the influence of genetics on these pathways is important. To this end, this review provides an up-to-date overview of the metabolism of anti-HIV therapeutics and the impact of genetic variation in drug metabolism and transport on the treatment of HIV. Future perspectives on and current challenges in pursuing personalized HIV treatment are also discussed.


Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 592
Author(s):  
Tran ◽  
Kelman ◽  
Ward ◽  
Westman

Feline immunodeficiency virus (FIV), feline calicivirus (FCV), and feline herpesvirus (FHV-1) are common viral infections of domestic cats in Australia. A study was performed to investigate the possible effect of area-based socioeconomic factors on the occurrence of FIV, FCV, and FHV-1 infection in Australian client-owned cats. A total of 1044 cases, reported to a voluntary Australian online disease surveillance system between January 2010 and July 2017, were analysed with respect to their postcode-related socioeconomic factors using the Socio-Economic Indexes For Areas (SEIFA). SEIFA consists of four different indexes which describe different aspects of socioeconomic advantage and disadvantage. Signalment details including age, sex, neuter status, and breed were also considered. A significant correlation was observed between areas of lower socioeconomic status and a higher number of reported cases of FIV infection for all four SEIFA indexes (p ≤ 0.0002). Postcodes with SEIFA indexes below the Australian median (“disadvantaged” areas) were 1.6–2.3 times more likely to have reported cases of FIV infection than postcodes with SEIFA indexes above the median (“advantaged” areas). In contrast, no correlation was observed between the number of reported cases of FCV or FHV-1 infection and any of the four SEIFA indexes (p > 0.05). When signalment data were analysed for the three infections, FIV-infected cats were more likely to be older (p < 0.00001), male (p < 0.0001), neutered (p = 0.03), and non-pedigree (p < 0.0001) compared to FCV and FHV-1 infected cats. Results from this study suggest that area-based disease control strategies, particularly in areas of social disadvantage, might be effective in reducing the prevalence of FIV infection in pet cats in Australia.


2005 ◽  
Vol 16 (3) ◽  
pp. 169-182 ◽  
Author(s):  
Prem L Sharma ◽  
Viktoria Nurpeisov ◽  
Raymond F Schinazi

The YXDD motif, where X is a variable amino acid, is highly conserved among various viral RNA-dependent DNA polymerases. Mutations in the YXDD motif can abolish enzymatic activity, alter the processivity and fidelity of enzymes and decrease virus infectivity. This review provides a summary of the significant documented studies on the YXDD motif of HIV-1, simian immunodeficiency virus, feline immunodeficiency virus and murine leukaemia virus and the impact of mutation that this motif has had on viral pathogenesis and drug treatment.


Author(s):  
Sarah A. Luse

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.


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