Aoki Yoshiyasu, Tosato Giovanna
Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Curr HIV Res. 2004 Oct;2(4):343-9. doi: 10.2174/1570162043351002.
HIV-1 infection predisposes to the development of specific types of cancer. Most cancers seen in the AIDS setting are related to oncogenic virus infections, such as Epstein-Barr virus (EBV), Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) and human papillomavirus (HPV). It is generally assumed that HIV-1 infection play a passive role in cancer development by impairing the host immune surveillance and increasing the risk of oncogenic virus infection. Recent insights, however, indicate that HIV-1 infection more actively promotes cancer growth. Experimental evidence has shown that HIV-1-encoded proteins can directly induce tumor angiogenesis and enhance KSHV transmission to target cells. Clinical evidence suggests that the oncogenicity of HPV is altered by the presence of HIV-1 infection irrespective of host immune status. The introduction of highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS whereas the impact of HAART is variable in EBV-related lymphoma and HPV-related cervical cancer, suggesting that additional factors are involved in the pathogenesis of these cancers. Understanding the direct and indirect roles of HIV-1 in the pathogenesis of neoplastic conditions could provide the rationale for prevention and development of new treatments for AIDS-associated malignancies.
人类免疫缺陷病毒1型(HIV-1)感染易引发特定类型的癌症。在艾滋病患者中出现的大多数癌症都与致癌病毒感染有关,如爱泼斯坦-巴尔病毒(EBV)、卡波西肉瘤(KS)相关疱疹病毒(KSHV)和人乳头瘤病毒(HPV)。通常认为,HIV-1感染通过损害宿主免疫监视并增加致癌病毒感染风险,在癌症发展中起被动作用。然而,最近的见解表明,HIV-1感染更积极地促进癌症生长。实验证据表明,HIV-1编码的蛋白质可直接诱导肿瘤血管生成,并增强KSHV向靶细胞的传播。临床证据表明,无论宿主免疫状态如何,HIV-1感染的存在都会改变HPV的致癌性。高效抗逆转录病毒疗法(HAART)的引入显著降低了KS的发病率,而HAART对EBV相关淋巴瘤和HPV相关宫颈癌的影响则各不相同,这表明这些癌症的发病机制中还涉及其他因素。了解HIV-1在肿瘤性疾病发病机制中的直接和间接作用,可为艾滋病相关恶性肿瘤的预防和新治疗方法的开发提供理论依据。