登革熱目前被認為是在熱帶和亞熱帶地區中最常見的蚊媒傳播疾病。全世界估計有25億人面臨感染的風險，每年約有5000萬至1億人得到登革熱。雖然大多數人不會出現明顯的症狀或只會有輕微的現象，像是頭痛，皮疹，肌肉和關節疼痛等，類似流感的症狀。少部分的人會發展成登革重症，如登革出血熱 (DHF)及登革休克症 (DSS)。而人體的皮膚是接觸任何病原體的第一道防線，其中皮膚細胞由多種細胞群組成，部分細胞群可以受到登革病毒（DENV）。為了更深入理解登革病毒感染的機制，我們利用登革病毒分別去感染三種皮膚細胞，HS68 (成纖維細胞)、A431（上皮細胞）和HaCAT（角質形成細胞）細胞來研究是否這些皮膚細胞可以受登革病毒感染。我們的結果顯示角質形成細胞和上皮細胞可以被登革病毒感染，而成纖維細胞無法支持登革病毒感染。我們也利用同為蚊媒傳播的茲卡病毒（ZIKV) 去感染細胞，令我們驚訝的是結果與登革病毒相反。我們還發現，與冷凍過後的骨與冷凍過後的骨髓 (Bone marrow) 相比，新鮮的骨髓很容易受到登革病毒感染。 從流式細胞儀分析結果顯示，新鮮骨髓中的幹細胞對登革病毒感染至關重要。進一步對皮膚細胞去做分析，發現到與其他細胞相比，角質形成細胞具有最多的幹細胞含量。而從角質形成細胞及上皮細胞中分選出來的幹細胞容易受到登革病毒的感染。通過蛋白質體學數據分析去鑑定這些皮膚細胞中的幹細胞群上可能作為登革病毒感染的受體，我們發現CD44可能是登革病毒感染幹細胞的受體。接著我們利用CD44的配體(ligand)透明質酸 (Hyuranic acid) 去阻斷CD44，再用登革病毒感染，結果顯示在加入透明質酸的組別中，病毒效價有顯著地降低。綜和以上結果，皮膚幹細胞容易受到登革病毒，而CD44可能是登革病毒感染皮膚幹細胞時的受體。

Dengue is currently regarded as the most common arthropod-borne viral disease transmitted by Aedes mosquito in tropical and subtropical areas. Worldwide, an estimated 2.5 billion people are at risk of infection, 50-100 million infections occurring each year. While most individuals either experience no symptoms or mild dengue fever a flu-like illness with headache, rash, muscle and joint pain. A small percentage go on to develop a life-threatening condition like dengue hemorrhagic fever (DHF). Human skin is the first line of defense against any pathogens upon mosquito bite and contains several populations of cells which could facilitate initial infection and systemic spread of dengue virus (DENV) infection. To better understand the pathogenesis of DENV infection, three skin cells, HS68 (fibroblast), A431 (epithelial) and HaCAT (keratinocyte) cells were utilized to investigate the permissiveness of DENV infection. Our results showed that keratinocyte and epithelial cells were permissive to DENV infection, while fibroblast cells were less likely to support DENV infection. To our surprised, the permissiveness of Zika virus (ZIKV) infection showed the opposite effects of DENV infection. We also found that fresh bone marrow (BM) were easily infected by DENV when compared to Frozen BM. FACS analysis revealed that stem cells in fresh BM were essential for DENV infection. Further analysis of skin cells revealed that HaCAT cells had the highest stem cell content compared to the other cells. Sorted stem cells from keratinocyte or epithelial cell were highly permissive to DENV infection. Identification of possible DENV receptors on stem cell population by proteomics data analysis revealed CD44 as putative DENV receptor in stem cells. Blocking of CD44 by antibody or ligand Hyuranic acid demonstrated a significant decrease in viral titer upon infection with DENV. In conclusion skin stem cells were highly permissive to DENV infection and CD44 is likely the bona fide receptor in skin stem cells for DENV.

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