CXCR4 expression during lymphopoiesis: implications for human immunodeficiency virus type 1 infection of the thymus.

Abstract:

:Human immunodeficiency virus type 1 (HIV-1) infection of the human thymus results in depletion of CD4-bearing thymocytes. This depletion is initially manifested in the immature CD4+/CD8+ thymocyte subset. To determine cellular factors involved in HIV infection in the thymus, we examined the expression of the recently identified viral coreceptor, CXCR4, on fresh human thymocytes and on human cells from SCID-hu (Thy/Liv) mice. CXCR4 is a member of the chemokine receptor family which is required along with CD4 for entry into the cell of syncytium-inducing (SI) HIV-1 strains. Our analyses show that CXCR4 expression is modulated during T-lymphoid differentiation such that immature thymocytes display an increased frequency and higher surface density of the coreceptor than do more mature cells. In addition, using an SI strain of HIV-1 which directs expression of a reporter protein on the surface of infected cells, we have found that the immature CD4+/CD8+ thymocytes that express the highest levels of both CD4 and CXCR4 are the cells that are preferentially infected and depleted by the virus in vitro. Thus, high levels of both primary receptor and coreceptor may allow efficient infection of the thymus by certain HIV-1 strains. This in part may explain the rapid disease progression seen in some HIV-infected children, where the thymus is actively involved in the production of new T lymphocytes.

journal_name

J Virol

journal_title

Journal of virology

authors

Kitchen SG,Zack JA

doi

10.1128/JVI.71.9.6928-6934.1997

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

6928-34

issue

9

eissn

0022-538X

issn

1098-5514

journal_volume

71

pub_type

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