CD4-Dependent and CD4-Independent Utilization of Coreceptors by Human Immunodeficiency Viruses Type 2 and Simian Immunodeficiency Viruses

Liu, Huiyu; Soda, Yasushi; Shimizu, Nobuaki; Haraguchi, Yuji; Jinno, Atsushi; Takeuchi, Yasuhiro; Hoshino, Hiroo

doi:10.1006/viro.2000.0623

Cited by 32 publications

(28 citation statements)

References 52 publications

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“…SIVman4 is a T-cell-line-adapted variant of SIVsmB670 (51). The coreceptor use of most of the virus isolates used in this study has been previously described (46,54) and is summarized in Table 1. All virus stocks were propagated in PBMCs purified from whole blood by density gradient centrifugation and stimulated for 2 days in phytohemagglutinin (1 g/ml) (Sigma) and for 2 days in human recombinant IL-2 (20 U/ml) (Roche, Inc.), with the exception of GUN-1v, which was passaged in the T-cell line MOLT4 clone 8.…”

Section: Methodsmentioning

confidence: 99%

Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

Willey

Reeves

Hudson

et al. 2003

J Virol

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The chemokine receptors CCR5 and CXCR4 are the major coreceptors for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). At least 12 other chemokine receptors or close relatives support infection by particular HIV and SIV strains on CD4؉ transformed indicator cell lines in vitro. However, the role of these alternative coreceptors in vivo is presently thought to be insignificant. Infection of cell lines expressing high levels of recombinant CD4 and coreceptors thus does not provide a true indication of coreceptor use in vivo. We therefore tested primary untransformed cell cultures that lack CCR5 and CXCR4, including astrocytes and brain microvascular endothelial cells (BMVECs), for naturally expressed alternative coreceptors functional for HIV and SIV infection. An adenovirus vector (Ad-CD4) was used to express CD4 in CD4 ؊ astrocytes and thus confer efficient infection if a functional coreceptor is present. Using a large panel of viruses with well-defined coreceptor usage, we identified a subset of HIV and SIV strains able to infect two astrocyte cultures derived from adult brain tissue. Astrocyte infection was partially inhibited by several chemokines, indicating a role for the chemokine receptor family in the observed infection. BMVECs were weakly positive for CD4 but negative for CCR5 and CXCR4 and were susceptible to infection by the same subset of isolates that infected astrocytes. BMVEC infection was efficiently inhibited by the chemokine vMIP-I, implicating one of its receptors as an alternative coreceptor for HIV and SIV infection. Furthermore, we tested whether the HIV type 1 and type 2 strains identified were able to infect peripheral blood mononuclear cells (PBMCs) via an alternative coreceptor. Several strains replicated in ⌬32/⌬32 CCR5 PBMCs with CXCR4 blocked by AMD3100. This AMD3100-resistant replication was also sensitive to vMIP-I inhibition. The nature and potential role of this alternative coreceptor(s) in HIV infection in vivo is discussed.

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Section: Methodsmentioning

confidence: 99%

Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

Willey

Reeves

Hudson

et al. 2003

J Virol

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“…In contrast, several primary HIV-2 and SIV isolates have been shown to enter cells in a CD4-independent way [81,148,168,[176][177][178][179].…”

Section: Cd4-independent Infectionmentioning

confidence: 96%

HIV-2 Interaction with Target Cell Receptors, or Why HIV-2 is Less Pathogenic than HIV-1

Azevedo‐Pereira¹

2013

Current Perspectives in HIV Infection

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“…(Schroder et al, 2002 (Dejucq et al, 1999;Dejucq, 2000), it may be difficult to estimate the exact coreceptor antagonisms. In contrast, NP-2 cells have been shown not to express any coreceptors for HIV Soda et al, 1999;Liu et al, 2000;Shimizu et al, 2000), suggesting that data obtained from NCK45 cells showed accurate coreceptor antagonisms. Indeed, coreceptor dependency of clinical isolates were easily evaluated in NP-2 derived cells (Witvrouw et al, 1992) (Chow et al, 1993;Schuetz et al, 1999;Villalba et al, 1999) (Chaillou et al, 2002;Zhu et al, 2004 …”

Section: The Activity Of Various Anti-hiv Agents Was Examined In Nck4mentioning

confidence: 97%

A Novel Colorimetric Assay for CXCR4 and CCR5 Tropic Human Immunodeficiency Viruses

Kajiwara

Kodama

Matsuoka

2006

Antivir Chem Chemother

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The majority of HIV isolated from infected patients uses CCR5 as a coreceptor (R5-HIV). Although R5-HIV fails to replicate efficiently in human transformed T-cell lines, HIV using CXCR4 (X4-HIV) can replicate well in such cell lines. Therefore, most of screening systems using the Tcell lines detect only X4-HIV replication. Here we report a new assay to monitor the replication of R5-as well as X4-HIV. An MTT assay using CD4-, CXCR4-, and CCR5-transduced human glioma NP-2 cells (NCK45 cells) was established and then compared with the representative assays including multinuclear activation of a galactosidase indicator assay (MAGI assay). The antiviral activities of not only an adsorption inhibitor and reverse transcriptase inhibitors but also a Tat antagonist in the NCK45 cells, were comparable to those obtained from the MTT assay using MT-4 cells or the MAGI assay. However, the activity of protease inhibitors (PIs) was underestimated, even though expressions of major multidrug resistant genes involved in efflux of PIs were comparable in MT-2, NP-2, and NCK45 cells. After cultivation of more than 6 months, NCK45 cells remained susceptible to HIV infection since NCK45 cells consistently expressed CD4, CXCR4, and CCR5. On the other hand, MAGI cells lost the CD4 expression during culture. Thus, this assay system can stably detect the replication of both X4-and R5-HIV, indicating that it should be useful for the evaluation of HIV replication and drug susceptibility.

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CD4-Dependent and CD4-Independent Utilization of Coreceptors by Human Immunodeficiency Viruses Type 2 and Simian Immunodeficiency Viruses

Cited by 32 publications

References 52 publications

Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

HIV-2 Interaction with Target Cell Receptors, or Why HIV-2 is Less Pathogenic than HIV-1

A Novel Colorimetric Assay for CXCR4 and CCR5 Tropic Human Immunodeficiency Viruses

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