Infection with HIV
Many of the clinical features of HIV infection can be ascribed
to the profound immune deficit that develops in infected
individuals. HIV is immunosuppressive because it infects cells of
the immune system and ultimately destroys them. An
understanding of this process is helpful in interpreting tests
used in monitoring the disease and may explain the failure of
immunotherapy and the difficulties in developing vaccines for
HIV.
The most obvious target of the virus is a subset of thymusderived
(T) lymphocytes carrying the surface molecule CD4,
which has been shown to bind the envelope glycoprotein of
HIV (gp120). CD4 is also present on a large proportion of
monocytes and macrophages, Langerhans’ cells of the skin and
dendritic cells of all tissues. More recently it has also become
clear that virus entry also requires co-receptors, most of which
are members of the seven transmembrane-spanning G proteincoupled
receptor family. In the immune system these principally
function as receptors for chemokines that orchestrate the
migration, differentiation and function of leucocytes during
immune responses. Two receptors, CCR5 and CXCR4, are
particularly important. CCR5 (R5) is widely expressed on
lymphocytes, macrophages, dendritic cells and cells of the
rectal, vaginal and cervical mucosae. Virus strains able to infect
primary macrophages (macrophage (M) or R5 tropic viruses) use
CCR5 as a co-receptor. Only R5 strains are detected early after
infection, while both R5 viruses and strains that infect T cells
and use CXCR4 (T or X4 tropic viruses) are found late in
infection. These data suggest that R5 strains are important for
transmission of HIV while X4 variants arise during the course
of infection and may be responsible for T-cell loss and disease
progression. Even stronger evidence that CCR5-using M tropic
viruses transmit infection, comes from the observation that
individuals homozygous for a 32 base pair deletion of CCR5
show greatly increased resistance to HIV infection. Several
other chemokine receptors have been shown capable of acting
as co-receptors in vitro and polymorphisms in CCR2 as well as
CCR5 and SDF1 (the ligand for CXCR4), are associated with
different rates of progression to AIDS.