Investigation of the cellular tropism and in vivo distribution of HIV-1

Abstract Since its discovery in 1983, HIV-1 has spread rapidly resulting in a global pandemic. Currently an estimated 40 million people are infected with the virus. Infection leads eventually to the acquired immunodeficiency syndrome (AIDS) and death. The symptoms of the syndrome are largely due to the devastating effect HIV has on the immune system. HIV has been the focus of an unprecedented amount of research however there are still many aspects of HIV pathogenesis which remain incompletely characterized. One area which continues to attract attention is HIV tropism. HIV requires two receptors- CD4 and a co-receptor- for infection. In vivo, HIV variants mainly use either CCR5 or CXCR4 as co-receptors and thus variants can be classified as either R5 (CCR5 using), X4 (CXCR4 using) or (R5X4) (dual tropic). However these classifications do not fully explain the differing abilities of variants to infect particular cell types. It is thought that other factors, such as receptor density or alternative receptors, may underlie observed differences in tropism. In addition to studying viral variants to investigate determinants of tropism, it is also possible to investigate post-mortem material from HIV infected individuals to characterize nature and cellular location of HIV variants. HIV can infect cells in the brain and this leads in some cases to HIV associated dementia (HAD). The presence of HIV in the brain poses a challenge to attempts to eradicate the virus as many drugs have poor CNS penetration. There have been concerns that sub-optimal levels of drugs in the CNS may support the evolution of drug resistant variants. Alternatively, low levels of drugs may allow growth of drug sensitive variants which could reseed the periphery if the drug regime was halted. Characterisation of the provirus present in post mortem brain material could lead to a better understanding of this issue. The virus in the brain appears to mainly infect microglia and macrophages however it is not clear to what extent other brain cells might be infected. Conflicting reports have emerged regarding the infection of astrocytes and neurons. Thus a method for separating the various brain cells which allows them to be tested for HIV could be valuable.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

2005

Author dc:creator

• Newman, Kirsty

Handle dc:identifier.uri

http://hdl.handle.net/1842/29916

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/29916