HIV tropism
Encyclopedia
HIV tropism refers to the cell type
that the human immunodeficiency virus (HIV) infects and replicates in. HIV tropism of a patient's virus is measured by the Trofile assay
.
HIV can infect a variety of cell
s such as CD4+ helper T-cells and macrophage
s that express the CD4
molecule on their surface. HIV-1 entry to macrophages and T helper cells is mediated not only through interaction of the virion envelope glycoproteins (gp120
) with the CD4 molecule on the target cells but also with its chemokine
coreceptors.
Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the beta-chemokine receptor CCR5
for entry and are thus able to replicate in macrophages and CD4+ T-cells . These strains are now called R5 viruses . The normal ligand
s for this receptor, RANTES
, macrophage inflammatory protein (MIP)-1-beta and MIP-1-alpha, are able to suppress HIV-1 infection in vitro. This CCR5 coreceptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype.
T-tropic isolates, or syncitia-inducing (SI) strains replicate in primary CD4+ T-cells as well as in macrophages and use the alpha-chemokine receptor, CXCR4
, for entry . These strains are now called X4 viruses . The alpha-chemokine, SDF-1, a ligand for CXCR4
, suppresses replication of T-tropic HIV-1 isolates. It does this by down regulating the expression of CXCR4 on the surface of these cells.
Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4R5. However, the use of coreceptor alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection.
Cell type
A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...
that the human immunodeficiency virus (HIV) infects and replicates in. HIV tropism of a patient's virus is measured by the Trofile assay
Trofile assay
The Trofile assay is a blood test that identifies the tropism of a patient's HIV.A molecular assay, Trofile was developed by Monogram Biosciences for use in HIV treatment. The assay's purpose is to identify the tropism of an individual patient's HIV strain – R5, X4, or a combination of these known...
.
HIV can infect a variety of cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s such as CD4+ helper T-cells and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s that express the CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
molecule on their surface. HIV-1 entry to macrophages and T helper cells is mediated not only through interaction of the virion envelope glycoproteins (gp120
Gp120
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons...
) with the CD4 molecule on the target cells but also with its chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
coreceptors.
Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the beta-chemokine receptor CCR5
CCR5
C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins...
for entry and are thus able to replicate in macrophages and CD4+ T-cells . These strains are now called R5 viruses . The normal ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
s for this receptor, RANTES
RANTES
Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. It is also known as RANTES .- Function :...
, macrophage inflammatory protein (MIP)-1-beta and MIP-1-alpha, are able to suppress HIV-1 infection in vitro. This CCR5 coreceptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype.
T-tropic isolates, or syncitia-inducing (SI) strains replicate in primary CD4+ T-cells as well as in macrophages and use the alpha-chemokine receptor, CXCR4
CXCR4
C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...
, for entry . These strains are now called X4 viruses . The alpha-chemokine, SDF-1, a ligand for CXCR4
CXCR4
C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...
, suppresses replication of T-tropic HIV-1 isolates. It does this by down regulating the expression of CXCR4 on the surface of these cells.
Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4R5. However, the use of coreceptor alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection.