Division of Basic Science and Vaccine Research, Institute of Human Virology, Baltimore, Maryland, United States of America.
PLoS One. 2010 Dec 20;5(12):e15562. doi: 10.1371/journal.pone.0015562.
We investigated the genetics of Fc receptors, which function as activating receptors on immune cells and help to control HIV through antibody-mediated cellular cytotoxicity. Thus, Fc receptors may be important for virus immunity but might also promote immune hyperactivation that would enhance infection.
METHODOLOGY/PRINCIPAL FINDINGS: We measured abundance of low and high activity alleles in two Fc receptor genes, FCGR2A and FCGR3A, for persons with HIV disease, natural virus suppressors (HIV+, without disease) and healthy controls to show whether genotypes were associated with infection and disease. Individuals homozygous for the high activity allele of FCGR3A (158VV) were predominantly found among HIV progressors and this group was also skewed toward higher allele frequencies for the V158 variant. Both of the HIV positive groups (progressors and natural virus suppressors) had significantly higher frequencies of the V158 allele compared with uninfected controls. There were no apparent associations among FCGR2A alleles and HIV status.
CONCLUSIONS/SIGNIFICANCE: Our results indicate that high activity alleles of FCGR3A may be risk factors for HIV infection or progression and we need to understand how allelic variants affect the balance between virus control and immune activation.
我们研究了 Fc 受体的遗传学，Fc 受体作为免疫细胞上的激活受体，通过抗体介导的细胞细胞毒性帮助控制 HIV。因此，Fc 受体可能对病毒免疫很重要，但也可能促进增强感染的免疫过度激活。
方法/主要发现：我们测量了 HIV 疾病患者、天然病毒抑制剂（HIV+，无疾病）和健康对照者的两个 Fc 受体基因 FCGR2A 和 FCGR3A 中的低活性和高活性等位基因的丰度，以显示基因型是否与感染和疾病有关。FCGR3A 基因（158VV）高活性等位基因纯合的个体主要存在于 HIV 进展者中，该组也偏向于 V158 变体的更高等位基因频率。与未感染者相比，这两个 HIV 阳性组（进展者和天然病毒抑制剂）的 V158 等位基因频率显著更高。FCGR2A 等位基因与 HIV 状态之间没有明显关联。
结论/意义：我们的结果表明，FCGR3A 的高活性等位基因可能是 HIV 感染或进展的危险因素，我们需要了解等位基因变异如何影响病毒控制和免疫激活之间的平衡。
