Combination Antiretroviral Therapy and Immunophenotype of Feline Immunodeficiency Virus.
Combination Antiretroviral Therapy and Immunophenotype of Feline Immunodeficiency Virus.
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DOI：
10.3390/v15040822
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发表时间：
2023-03-24
期刊：
影响因子：
--
通讯作者：
Miller CA
中科院分区：
文献类型：
--
作者：
Kim J;Behzadi ES;Nehring M;Carver S;Cowan SR;Conry MK;Rawlinson JE;VandeWoude S;Miller CA
猫免疫缺陷病毒（FIV）导致猫进行性免疫功能障碍，类似于人类免疫缺陷病毒（HIV）。虽然联合抗逆转录病毒疗法（cART）对HIV有效，但没有明确的治疗方法来改善FIV猫的临床结局。因此，本研究评估了cART（2.5 mg/kg度鲁特韦; 20 mg/kg替诺福韦; 40 mg/kg恩曲他滨）在FIV感染家猫中的药代动力学和临床结局。无特定病原体的猫实验性感染FIV，并给予cART或安慰剂治疗（各n = 6）18周，而n = 6只未感染的未感染猫作为对照。采集下颌淋巴结的血液、唾液和细针抽吸物，通过数字液滴PCR定量病毒和前病毒载量，并通过流式细胞术评估淋巴细胞免疫表型。cART改善了FIV感染的猫的血液恶液质，其在第16周时正常化，而安慰剂猫仍然是血吸虫病，尽管在血液或唾液中没有观察到病毒血症的显著差异。与安慰剂猫相比，cART治疗猫表现出Th 2免疫表型，CD 4 + CCR 4+细胞比例增加，与安慰剂治疗猫相比，cART恢复了Th 17细胞。在cART药物中，度鲁特韦是最稳定、最持久的。这些发现为FIV感染猫的新型cART制剂提供了重要见解，并强调了它们作为潜在动物模型的作用，以评估cART对慢病毒感染和免疫失调的影响。
Feline Immunodeficiency Virus (FIV) causes progressive immune dysfunction in cats similar to human immunodeficiency virus (HIV) in humans. Although combination antiretroviral therapy (cART) is effective against HIV, there is no definitive therapy to improve clinical outcomes in cats with FIV. This study therefore evaluated pharmacokinetics and clinical outcomes of cART (2.5 mg/kg Dolutegravir; 20 mg/kg Tenofovir; 40 mg/kg Emtricitabine) in FIV-infected domestic cats. Specific pathogen free cats were experimentally infected with FIV and administered either cART or placebo treatments (n = 6 each) for 18 weeks, while n = 6 naïve uninfected cats served as controls. Blood, saliva, and fine needle aspirates from mandibular lymph nodes were collected to quantify viral and proviral loads via digital droplet PCR and to assess lymphocyte immunophenotypes by flow cytometry. cART improved blood dyscrasias in FIV-infected cats, which normalized by week 16, while placebo cats remained neutropenic, although no significant difference in viremia was observed in the blood or saliva. cART-treated cats exhibited a Th2 immunophenotype with increasing proportions of CD4+CCR4+ cells compared to placebo cats, and cART restored Th17 cells compared to placebo-treated cats. Of the cART drugs, dolutegravir was the most stable and long-lasting. These findings provide a critical insight into novel cART formulations in FIV-infected cats and highlight their role as a potential animal model to evaluate the impact of cART on lentiviral infection and immune dysregulation.
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影响因子：
3.2
作者：
Beck SE;Queen SE;Metcalf Pate KA;Mangus LM;Abreu CM;Gama L;Witwer KW;Adams RJ;Zink MC;Clements JE;Mankowski JL
通讯作者：
Mankowski JL
影响因子：
1.5
作者：
Aleebrahim-Dehkordi E;Molavi B;Mokhtari M;Deravi N;Fathi M;Fazel T;Mohebalizadeh M;Koochaki P;Shobeiri P;Hasanpour-Dehkordi A
通讯作者：
Hasanpour-Dehkordi A
影响因子：
5.4
作者：
Dean, GA;Pedersen, NC
通讯作者：
Pedersen, NC
影响因子：
--
作者：
Anderson EM;Maldarelli F
通讯作者：
Maldarelli F
影响因子：
1.8
作者：
Ritchey JW;Levy JK;Bliss SK;Tompkins WA;Tompkins MB
通讯作者：
Tompkins MB