Mapping SHIV infection in the body, 2018 - Wellcome Photography Prize 2019 (bottom right, cropped)

HIV tropism refers to the

cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cells, ...

in which the human immunodeficiency virus (

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

) infects and replicates. HIV

tropism A tropism is a biological phenomenon, indicating growth or turning movement of a biological organism, usually a plant, in response to an environmental stimulus. In tropisms, this response is dependent on the direction of the stimulus (as oppose ...

of a patient's virus is measured by the

Trofile assay HIV tropism refers to the cell type in which the human immunodeficiency virus (HIV) infects and replicates. HIV tropism of a patient's virus is measured by the Trofile assay. HIV can infect a variety of cells such as CD4+ helper T-cells and ma ...

. HIV can infect a variety of

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s such as CD4+ helper T-cells and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

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 Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from ...

) with the CD4 molecule on the target cells but also with its

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

coreceptors. Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the beta-chemokine receptor

CCR5 C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. In humans, the ''CCR5'' gene that encodes the CCR5 pro ...

for entry and are thus able to replicate in macrophages and CD4+ T-cells. These strains are now called R5 viruses. The normal

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

s for this receptor—

RANTES Chemokine (C-C motif) ligand 5 (also CCL5) is a protein which in humans is encoded by the ''CCL5'' gene. The gene has been discovered in 1990 by ''in situ'' hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTES ...

macrophage inflammatory protein Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now (according to the new nomenclature) officially named CCL3 and CCL4, r ...

(MIP)-1β and MIP-1α—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 A syncytium (; plural syncytia; from Greek: σύν ''syn'' "together" and κύτος ''kytos'' "box, i.e. cell") or symplasm is a multinucleate cell which can result from multiple cell fusions of uninuclear cells (i.e., cells with a single nucleus) ...

-inducing (SI) strains replicate in primary CD4+ T-cells as well as in macrophages and use the alpha-chemokine receptor,

CXCR4 C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha-chemokin ...

, 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 downregulating 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 a coreceptor alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection.

Trofile assay

The Trofile assay is a blood test that identifies the tropism of a patient's

. A molecular

assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...

, Trofile was developed by Monogram Biosciences for use in

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 as dual/mixed (D/M). The results show whether the patient is infected with virus that enters cells using the R5 co-receptor, the X4 co-receptor, or both (dual/mixed). Patients with strains of HIV that prefer the R5 receptor tend to remain healthy longer than those with the strains that prefer X4. However, over the course of the disease, a patient's viral population may undergo a "tropism switch" from R5 to X4.

References

External links

HIVcoPred
A server for prediction of HIV coreceptor usage (CCR5)
PLoS ONE 8(4): e61437
* Monogram Biosciences' Trofile assay: *
Monogram Biosciences' Trofile assay website
*
Four Studies Affirm Significance Of Monogram's Trofile HIV Co-Receptor Tropism Assay
from Medical News Today, August 14, 2006 *
Scientific Data Highlights Pivotal Role Of Monogram's Molecular Diagnostics In Development And Use Of New HIV Treatments
from Medical News Today, March 7, 2007 {{DEFAULTSORT:Hiv Tropism HIV/AIDS