Abstract:
Most viral infections can be self-limited, with no requirement for medical intervention. However, the same viruses can cause severe diseases in patients with compromised immunity due to single-gene diseases, acquired immune deficiency syndrome, or hematologic malignancies or those receiving immunosuppressive drugs. Occasionally, these immunocompromised patients harbor >1 infectious agent, requiring several concomitant diagnostic tests. We have developed, to our knowledge, a previously unreported whole-transcriptome sequencing-based pipeline that allows virome profiling, quantitation, and expression pattern analysis of 926 distinct viruses by sequencing of RNA isolated from a single lesional skin biopsy. This pipeline can also explore host genetics if there is a Mendelian predisposition to infection. We applied this pipeline to 6 Iranian patients with viral-induced skin lesions associated with immune deficiency secondary to HIV, human T-lymphotropic virus 1, chronic lymphocytic leukemia, and post transplant immunosuppression. In 5 cases, definitive human papillomavirus infections were identified, some caused by multiple viral types. In addition to human papillomavirus, coinfection with other viruses (Merkle cell polyomavirus, cytomegalovirus, and human herpesvirus 4) was detected in some lesions. In 1 case, whole-transcriptome sequencing validated the clinical diagnosis of adult T-cell leukemia/lymphoma in a patient with an initial diagnosis of mycosis fungoides/Sézary syndrome. These findings attest to the power of whole-transcriptome sequencing in profiling the cutaneous virome in the context of compromised immunity.
摘要:
大多数病毒感染可以自我限制,不需要医疗干预。然而,由于单基因疾病,相同的病毒会导致免疫力低下的患者严重疾病,获得性免疫缺陷综合征,或血液系统恶性肿瘤或接受免疫抑制药物的患者。偶尔,这些免疫功能低下的患者携带>1个感染因子,需要几个伴随的诊断测试。我们开发了,根据我们的知识,一个以前未报告的基于全转录组测序的管道,允许病毒谱,定量,通过对从单个病变皮肤活检中分离的RNA进行测序,对926种不同病毒进行表达模式分析。如果有孟德尔感染倾向,这个管道也可以探索宿主遗传学。我们将此管道应用于6名伊朗患者,这些患者患有病毒引起的皮肤病变,这些患者与继发于HIV的免疫缺陷有关,人类嗜T淋巴细胞病毒1,慢性淋巴细胞白血病,移植后免疫抑制.在5个案例中,确定人乳头瘤病毒感染,有些是由多种病毒引起的。除了人乳头瘤病毒,与其他病毒(Merkle细胞多瘤病毒,巨细胞病毒,在某些病变中检测到人疱疹病毒4)。在1种情况下,全转录组测序验证了1例初次诊断为真菌病/Sézary综合征的成人T细胞白血病/淋巴瘤的临床诊断.这些发现证明了全转录组测序在免疫受损的情况下对皮肤病毒体进行分析的能力。