Monocytes and HIV Reservoirs

巨噬细胞系的细胞，免疫系统的清道夫细胞，攻击入侵的生物体和其他受感染的细胞，是HIV感染的重要目标，是当病毒在人与人之间传播时最先被感染的细胞之一，并在整个疾病进展过程中充当病毒的储存库。血液中的单核细胞，组织中巨噬细胞的替代者，对艾滋病毒感染并不敏感，但我们和其他人已经表明，在感染者的一生中，少数人会感染艾滋病毒，尽管经过多年的有效联合药物治疗，血液中的病毒量减少到无法检测的水平，但他们仍然受到感染。我们有证据表明，单核细胞的某个子集可能优先感染艾滋病毒，并可能显着有助于其在体内的持久性。已知该亚群在对某些感染（可能包括HIV）和炎症期间的反应中扩大。我们已经证明，这些细胞在艾滋病毒感染者的大脑中积累，特别是那些患有艾滋病相关痴呆症的人。在这个项目中，我们将在血液中培养这些细胞，并测试我们的假设，即在这个单核细胞亚群中持续感染在HIV疾病的过程中起着重要作用，并有助于HIV感染的持续性和目前可用的治疗方法根除它的失败。

Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers are infected throughout an infected person's life and that they remain infected despite years of treatment with potent combination drug therapies which reduce the amount of virus in the blood to undetectable levels. We have evidence that suggests that a certain subset of monocytes may be preferentially infected with HIV and may contribute significantly to its persistence in the body. This subset is known to be expanded in response to certain infections, probably including HIV, and during inflammation. We have shown that these cells accumulate in the brains of HIV-infected people especially those with AIDS related dementia. In this project we will characterise these cells in the blood and test our hypothesis that ongoing infection in this subset of monocytes plays an important role in the course of HIV disease and contributes to the persistence of HIV infection and the failure of currently available therapies to eradicate it.