Discovery of a New Human Polyomavirus Associated with <i>Trichodysplasia Spinulosa</i> in an Immunocompromized Patient

The Polyomaviridae constitute a family of small DNA viruses infecting a variety of hosts. In humans, polyomaviruses can cause infections of the central nervous system, urinary tract, skin, and possibly the respiratory tract. Here we report the identification of a new human polyomavirus in plucked facial spines of a heart transplant patient with trichodysplasia spinulosa, a rare skin disease exclusively seen in immunocompromized patients. The trichodysplasia spinulosa-associated polyomavirus (TSV) genome was amplified through rolling-circle amplification and consists of a 5232-nucleotide circular DNA organized similarly to known polyomaviruses. Two putative “early” (small and large T antigen) and three putative “late” (VP1, VP2, VP3) genes were identified. The TSV large T antigen contains several domains (e.g. J-domain) and motifs (e.g. HPDKGG, pRb family-binding, zinc finger) described for other polyomaviruses and potentially involved in cellular transformation. Phylogenetic analysis revealed a close relationship of TSV with the Bornean orangutan polyomavirus and, more distantly, the Merkel cell polyomavirus that is found integrated in Merkel cell carcinomas of the skin. The presence of TSV in the affected patient's skin was confirmed by newly designed quantitative TSV-specific PCR, indicative of a viral load of 105 copies per cell. After topical cidofovir treatment, the lesions largely resolved coinciding with a reduction in TSV load. PCR screening demonstrated a 4% prevalence of TSV in an unrelated group of immunosuppressed transplant recipients without apparent disease. In conclusion, a new human polyomavirus was discovered and identified as the possible cause of trichodysplasia spinulosa in immunocompromized patients. The presence of TSV also in clinically unaffected individuals suggests frequent virus transmission causing subclinical, probably latent infections. Further studies have to reveal the impact of TSV infection in relation to other populations and diseases.多瘤病毒科（Polyomaviridae）是一类感染多种宿主的小型DNA病毒家族。在人类中，多瘤病毒可引发中枢神经系统、尿路、皮肤，乃至可能的呼吸道感染。本研究报道了从一例罹患棘状毛发角化病（trichodysplasia spinulosa，一种仅见于免疫功能低下患者的罕见皮肤病）的心脏移植患者的面部拔除毛囊样本中，鉴定出一种新型人类多瘤病毒的过程。这种与棘状毛发角化病相关的多瘤病毒（TSV）基因组通过滚环扩增（rolling-circle amplification）得以扩增，其全长为5232个核苷酸，呈环状DNA结构，基因组组织形式与已知多瘤病毒相似。研究人员鉴定出2个推定的"早期"基因（小T抗原与大T抗原）以及3个推定的"晚期"基因（VP1、VP2、VP3）。TSV的大T抗原包含多个结构域（如J结构域）与基序（如HPDKGG、pRb家族结合基序、锌指基序），这些元件在其他多瘤病毒中已有报道，且可能参与细胞转化过程。系统发育分析显示，TSV与婆罗洲猩猩多瘤病毒亲缘关系较近，而与整合于皮肤默克尔细胞癌中的默克尔细胞多瘤病毒（Merkel cell polyomavirus）亲缘关系较远。通过新设计的TSV特异性定量聚合酶链反应，证实了受感染患者皮肤中存在TSV，其病毒载量约为每细胞10^5个拷贝。经局部西多福韦（cidofovir）治疗后，皮损显著消退，且该过程与TSV载量的降低相吻合。聚合酶链反应筛查显示，在一组无明显病症的免疫抑制移植受者中，TSV的携带率为4%。综上，本研究发现并鉴定了一种新型人类多瘤病毒，其可能为免疫功能低下患者罹患棘状毛发角化病的致病原。在临床未出现病症的个体中也检测到TSV的存在，提示该病毒存在频繁传播，可引发亚临床、大概率为潜伏性的感染。后续研究需进一步阐明TSV感染对其他人群及相关疾病的影响。