Biology Reference
In-Depth Information
nucleus and, under the direction of the viral enzyme integrase, becomes ran-
domly integrated with host cell genome. This integrated form of HIV-1 is re-
ferred to as HIV-1 proviral DNA, and remains latent until transcription is
initiated by an appropriate cell stimulus. In general, HIV-1 infection of CD4
T lymphocytes is characterized by active HIV-1 replication, whereas HIV-1
infection of resting T lymphocytes or monocyte-macrophages is predominantly
latent or persistent with limited viral replication.
HIV-1 transcription is initiated by the activation and binding of host cell
transcription factors such as NF-kB/Rel to speci®c binding sites in the HIV-1
LTR region of the viral genome. Binding to the HIV-1 LTR promotor site then
activates host cell RNA polymerase II. Following cell activation, the 2.0-kb
HIV-1 regulatory genes (tat, nef, rev) are transcribed ®rst and transported to the
cytoplasm. Under the direction of the regulatory proteins, the HIV-1 structural
and enzymatic genes are then transcribed as precursors and transported to the
cytoplasm where these products undergo cellular protease cleavage. The HIV-1
viral nucleocapsid components, full-length HIV-1 RNA, and HIV-1 enzymes
then assemble in the cytoplasm, are transported to the inner surface of the cell
membrane, and then released from the infected cells by a process of budding
from cell plasma membrane, acquiring the host cell lipid bilayer as the virion
coat. A variety of factors can stimulate or enhance HIV replication, including
cytokines, mitogens, and infectious agents. Currently, there are no vaccines that
prevent HIV-1 infection and no drugs that eliminate or cure HIV-1 infection in
patients. Most of the available antiretroviral drugs that are currently used to
control HIV-1 infection are targeted to inhibit the function of HIV-1 RT and
HIV-1 protease, and thus limit viral replication.
In the context of AM, other important characteristics of HIV-1 isolates de-
serve mention. In general, HIV-1 infection of CD4
T lymphocytes results
in cytotoxic e¨ects to the cells, whereas HIV-1 infection of monocyte-macro-
phages are resistant to the cytopathic e¨ects of HIV-1 infection. Evidence sug-
gests that HIV-1 evolves di¨erently in di¨erent anatomical compartments of
the same individuals, suggesting local in¯uences may contribute signi®cantly to
HIV-1 replication and evolution and may in¯uence drug susceptibility. Finally,
most currently available drugs require active HIV-1 replication for e½cacy, and
whether these agents will a¨ect long-lived and latently infected cells such as
AM remains to be established.
ALVEOLAR MACROPHAGES IN HIV-1 DISEASE
Several investigators have provided important insights into the function of AM
in the lungs of HIV-infected individuals and the in¯uence of HIV-1 infection on
AM function. Much of the data has been obtained by ¯ow cytometry method-
ology, which has allowed the detailed investigation of various AM parameters
(Table 10.1).
