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Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity to Restriction Factors
Akatsuki Saito - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity to Restriction Factors
ผู้แต่ง / หัวหน้าโครงการ (EN): Akatsuki Saito
บทคัดย่อ (EN): TRIM5a and MxB are known as restriction factors that inhibit the early step of intracellular HIV-1 replication cycle. Both factors are believed to interact with the incoming virus core to suppress HIV-1 infection. The extreme diversity of HIV-1 is thought to be a consequence of its propensity to mutate to escape immune responses and host restriction factors. We recently determined the capsid sequences for 144 HIV-1 CRF01_AE viruses obtained in Thailand from 2005 to 2011. In this study, we further analyzed the amino acid variations among the capsid sequences of 204 HIV-1 CRF01_AE obtained in Thailand and China, including 84 of the aforementioned 144 viruses, to detect mutations permitting escape from restriction by host factors. We found a characteristic combination of E79D, V83T, and H87Q in sequences from Chinese viruses and subsequently showed that this combination conferred partial resistance to MxB. Interestingly, this combination conferred resistance to human TRIM5a as well. The H87Q mutation alone conferred resistance to MxB in the CRF01_AE background, but not in subtype B virus. In contrast, the H87Q mutation alone conferred resistance to human TRIM5a in both the CFR01_AE and subtype B backgrounds. BLAST analysis revealed the presence of the E79D, V83T, and H87Q combination in CRF01_AE viruses isolated not only in China but also in many other countries. Although the mechanistic details as well as precise role of MxB antiviral activity in infected individuals remain to be clarified, our data suggest an interaction between MxB and the HIV-1 capsid in vivo.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): http://nih.dmsc.moph.go.th/research/showimgdetil.php?id=518
เผยแพร่โดย (EN): 1 Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 2 Thailand-Japan Research Collaboration Center on Emerging and Re-Emerging Infections (RCC-ERI), Osaka University, Nonthaburi,Thailand. 3 National Institute of Health, Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand.
คำสำคัญ (EN): TRIM5a; MxB; CRF01_AE; capsid
เจ้าของลิขสิทธิ์ (EN): National Institute of Health, Department of Medical Science
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Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity to Restriction Factors
Akatsuki Saito
1 Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 2 Thailand-Japan Research Collaboration Center on Emerging and Re-Emerging Infections (RCC-ERI), Osaka University, Nonthaburi,Thailand. 3 National Institute of Health, Department of Medical Science, Ministry of Public Health, Nonthaburi, Thailand.
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