Infection of a Simian B Cell Line by Human and Simian Immunodeficiency Viruses

Ridolfi, Barbara; Titti, Fausto; Fulgenzi, Domenico; Maggiorella, Maria Teresa; Tinari, Antonella; Superti, Fabiana; Parolin, Cristina; Ensoli, Barbara; Borsetti, Alessândra

doi:10.1089/0889222041524652

Cited by 3 publications

(9 citation statements)

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“…The origin and the characterization of the F6 cells were previously described (Ridolfi et al, 2004). F6 cells are a CD4-negative cynomolgus monkey B cell line able to support HIV-1 infection.…”

Section: Resultsmentioning

confidence: 99%

“…F6 cells are a CD4-negative cynomolgus monkey B cell line able to support HIV-1 infection. Concerning chemokine receptors, the CXCR4 is expressed at high levels (99%), whereas the CCR5 expression level is below 1% (Ridolfi et al, 2004). To obtain chronically infected cells, the F6 cell line was infected with low dose of replication competent HXBc2/HIV-1 (0.01 TCID 50 /cell) and the release of infectious progeny virus was detected by measuring the levels of viral p24 in the culture supernatants at different time points post-infection (p.i.).…”

Section: Resultsmentioning

confidence: 99%

“…The BLCL are Herpesvirus papio-transformed cynomolgus monkey B lymphoblastoid cell line. HIV-1 chronically infected F6 cells (F6/HIV-1) were derived from the F6 monkey B cell line (Titti et al, 2002;Ridolfi et al, 2004) as previously described. HSC-F4, BLCL and F6/HIV-1 cells were maintained in (RPMI 1640, Invitrogen) supplemented with 20% FCS and split every 4 days to prevent overgrowth.…”

Section: Cell Culturesmentioning

confidence: 99%

“…The pelleted virus and cells were lysed in radioimmunoprecipitation assay (RIPA) buffer and immunoprecipitated with an HIV-1 positive human serum. Proteins were separated on a 12% resolving gel by SDS-PAGE as previously described (Ridolfi et al, 2004).…”

Section: Viral Protein Analysismentioning

confidence: 99%

“…These viruses could provide extremely valuable new tools for the development of more authentic animal models of human AIDS. In this context, our goal was to derive a monkey cell line chronically infected by HIV-1 starting from a de novo infection of a macaque B cell line (F6), that was previously described by our group to be susceptible to HIV-1 infection (Ridolfi et al, 2004). Virus derived from HIV-1 chronically infected F6 cells was able to infect human T cell lines and peripheral blood mononuclear cells (PBMCs), showing a replication ability lower compared to that of the wild type virus, but it failed to infect cynomolgus monkey PBMCs and monkey cell lines.…”

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confidence: 99%

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Generation of a human immunodeficiency virus type 1 chronically infected monkey B cell line expressing low levels of endogenous TRIM5α

Ridolfi

Catone

Sgarbanti

et al. 2009

Journal Cellular Physiology

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Several innate cellular antiviral factors exist in mammalian cells that prevent the replication of retroviruses. Among them, the tripartite motif protein (TRIM)5alpha has been shown to block human immunodeficiency virus type 1 (HIV-1) infection in several types of Old World monkey cells. Here we report a novel HIV-1 chronically infected monkey B cell line, F6/HIV-1, characterized by very low levels of TRIM5alpha expression that allows HIV-1 to overcome the restriction. Virus produced by F6/HIV-1 cells fails to infect monkey cells but retains the ability to infect human peripheral blood mononuclear cells (PBMCs) and T cell lines, although with a reduced infectivity compared to the input virus. Ultrastructural analyses revealed the presence of budding virions at the F6/HIV-1 cells plasma membrane characterized by a typical conical core shell. To our knowledge F6/HIV-1 is the first monkey cell line chronically infected by HIV-1 and able to release infectious particles thus representing a useful tool to gain further insights into the molecular mechanisms of HIV-1 pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Viral Protein Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Generation of a human immunodeficiency virus type 1 chronically infected monkey B cell line expressing low levels of endogenous TRIM5α

Ridolfi

Catone

Sgarbanti

et al. 2009

Journal Cellular Physiology

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Alternate NF-κB-Independent Signaling Reactivation of Latent HIV-1 Provirus

Acchioni

Remoli

Marsili

et al. 2019

J Virol

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Current combination antiretroviral therapies (cART) are unable to eradicate HIV-1 from infected individuals because of the establishment of proviral latency in long-lived cellular reservoirs. The shock-and-kill approach aims to reactivate viral replication from the latent state (shock) using latency-reversing agents (LRAs), followed by the elimination of reactivated virus-producing cells (kill) by specific therapeutics. The NF-κB RelA/p50 heterodimer has been characterized as an essential component of reactivation of the latent HIV-1 long terminal repeat (LTR). Nevertheless, prolonged NF-κB activation contributes to the development of various autoimmune, inflammatory, and malignant disorders. In the present study, we established a cellular model of HIV-1 latency in J-Lat CD4+ T cells that stably expressed the NF-κB superrepressor IκB-α 2NΔ4 and demonstrate that conventional treatments with bryostatin-1 and hexamethylenebisacetamide (HMBA) or ionomycin synergistically reactivated HIV-1 from latency, even under conditions where NF-κB activation was repressed. Using specific calcineurin phosphatase, p38, and MEK1/MEK2 kinase inhibitors or specific short hairpin RNAs, c-Jun was identified to be an essential factor binding to the LTR enhancer κB sites and mediating the combined synergistic reactivation effect. Furthermore, acetylsalicylic acid (ASA), a potent inhibitor of the NF-κB activator kinase IκB kinase β (IKK-β), did not significantly diminish reactivation in a primary CD4+ T central memory (TCM) cell latency model. The present work demonstrates that the shock phase of the shock-and-kill approach to reverse HIV-1 latency may be achieved in the absence of NF-κB, with the potential to avoid unwanted autoimmune- and or inflammation-related side effects associated with latency-reversing strategies. IMPORTANCE The shock-and-kill approach consists of the reactivation of HIV-1 replication from latency using latency-reversing agents (LRAs), followed by the elimination of reactivated virus-producing cells. The cellular transcription factor NF-κB is considered a master mediator of HIV-1 escape from latency induced by LRAs. Nevertheless, a systemic activation of NF-κB in HIV-1-infected patients resulting from the combined administration of different LRAs could represent a potential risk, especially in the case of a prolonged treatment. We demonstrate here that conventional treatments with bryostatin-1 and hexamethylenebisacetamide (HMBA) or ionomycin synergistically reactivate HIV-1 from latency, even under conditions where NF-κB activation is repressed. Our study provides a molecular proof of concept for the use of anti-inflammatory drugs, like aspirin, capable of inhibiting NF-κB in patients under combination antiretroviral therapy during the shock-and-kill approach, to avoid potential autoimmune and inflammatory disorders that can be elicited by combinations of LRAs.

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Phosphatidylcholine Liposomes Down-Modulate CD4 Expression Reducing HIV Entry in Human Type-1 Macrophages

et al. 2022

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A strategy adopted to combat human immunodeficiency virus type-1 (HIV-1) infection is based on interfering with virus entry into target cells. In this study, we found that phosphatidylcholine (PC) liposomes reduced the expression of the CD4 receptor in human primary type-1 macrophages but not in CD4+ T cells. The down-regulation was specific to CD4, as any effect was not observed in CCR5 membrane expression. Moreover, the reduction of membrane CD4 expression required the Ca2+-independent protein kinase C (PKC), which in turn mediated serine phosphorylation in the intracytoplasmic tail of the CD4 receptor. Serine phosphorylation of CD4 was also associated with its internalization and degradation in acidic compartments. Finally, the observed CD4 downregulation induced by PC liposomes in human primary macrophages reduced the entry of both single-cycle replication and replication competent R5 tropic HIV-1. Altogether, these results show that PC liposomes reduce HIV entry in human macrophages and may impact HIV pathogenesis by lowering the viral reservoir.

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Infection of a Simian B Cell Line by Human and Simian Immunodeficiency Viruses

Cited by 3 publications

References 35 publications

Generation of a human immunodeficiency virus type 1 chronically infected monkey B cell line expressing low levels of endogenous TRIM5α

Generation of a human immunodeficiency virus type 1 chronically infected monkey B cell line expressing low levels of endogenous TRIM5α

Alternate NF-κB-Independent Signaling Reactivation of Latent HIV-1 Provirus

Phosphatidylcholine Liposomes Down-Modulate CD4 Expression Reducing HIV Entry in Human Type-1 Macrophages

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