Asymmetric HIV-1 co-receptor use and replication in CD4+ T lymphocytes

Samanta A Mariani,Guido Poli,Elisa Vicenzi

doi:10.1186/1479-5876-9-s1-s8

Abstract

Susceptibility to infection by the human immunodeficiency virus type-1 (HIV-1), both in vitro and in vivo, requires the interaction between its envelope (Env) glycoprotein gp120 Env and the primary receptor (R), CD4, and Co-R, either CCR5 or CXCR4, members of the chemokine receptor family. CCR5-dependent (R5) viruses are responsible for both inter-individual transmission and for sustaining the viral pandemics, while CXCR4-using viruses, usually dualtropic R5X4, emerge in ca. 50% of individuals only in the late, immunologically suppressed stage of disease. The hypothesis that such a major biological asymmetry is explained exclusively by the availability of cells expressing CCR5 or CXCR4 is challenged by several evidences. In this regard, binding of the HIV-1 gp120 Env to the entry R complex, i.e. CD4 and a chemokine R, leads to two major events: virion-cell membrane fusion and a cascade of cell signaling. While the fusion/entry process has been well defined, the role of R/Co-R signaling in the HIV-1 life cycle has been less characterized. Indeed, depending on the cellular model studied, the capacity of HIV-1 to trigger a flow of events favoring either its own latency or replication remains a debated issue. In this article, we will review the major findings related to the role of HIV R/Co-R signaling in the steps following viral entry and leading to viral spreading in CD4+ T lymphocytes.

Highlights

Infection with the human immunodeficiency virus 1 type1 (HIV-1) causes a severe and selective depletion of the CD4+ T lymphocytes both in vivo and in vitro
In 1984, CD4 was described as main receptor (R) for HIV-1 entry into this subset of T lymphocytes [1,2,3]
receptor family. CCR5-dependent (R5) HIV-1 replicated more efficiently than the X4 viruses in peripheral blood derived primary CD4+ T cells expressing in vivo levels of CCR5 on their surface [42]

Summary

Introduction

Infection with the human immunodeficiency virus 1 type (HIV-1) causes a severe and selective depletion of the CD4+ T lymphocytes both in vivo and in vitro. The superior efficiency of R5 vs X4 viruses in DC-T cell spreading was shown to be dependent upon the state of activation of CD4+ T cells and not consequent of a higher efficiency by virus to infect DC [41] (Table 1) In this regard, R5 HIV-1 replicated more efficiently than the X4 viruses in peripheral blood derived primary CD4+ T cells expressing in vivo levels of CCR5 on their surface [42]. BSCI blocked HIV1 replication, without inhibiting gp120 Env interaction with CCR5 or CXCR4 in THP-1 monocytic and Jurkat T lymphocytic cell lines, respectively [79] These findings together suggest that chemokine Co-R signaling is not required for the efficient entry of R5 and X4 viruses into target cells, it likely plays an important role in order to guarantee efficient virus replication by affecting one or more post-entry steps in the virus life cycle. No studies has yet determined whether CXCR4 signaling can confer resistance to apoptosis in monocyte/macrophages independently of immune activation

Conclusion

17. Sprent J

43. O’Garra A