INHIBITORY AND ENHANCING EFFECTS OF IFN-γ AND IL-4 ON SHIVKUREPLICATION IN RHESUS MACAQUE MACROPHAGES: CORRELATION BETWEEN TH2CYTOKINES AND PRODUCTIVE INFECTION IN TISSUE MACROPHAGES DURING LATE-STAGE INFECTION

Buch, Shilpa; Pinson, David M.; King, Christopher L.; Raghavan, Ravi; Hou, Yueping; Li, Zhuang; Adany, Istvan; Hicks, Andre; Villinger, François; Kumar, Anil; Narayan, Opendra

doi:10.1006/cyto.2000.0829

Cited by 24 publications

(28 citation statements)

References 33 publications

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“…This concept was illustrated in a previous report in which intratracheal inoculation of SHIV-infected macaques with S. mansoni eggs resulted in development of granulomas that comprised of macrophages that became productively infected with the virus. 17 In the present study we speculate that the synergy between opportunistic pathogen(s) and SHIV could have resulted in increased numbers of virusinfected macrophages in the lungs. This, in turn, would lead to enhanced production of MCP-1 and CXCL10, both of which are known to be induced in virus-infected cells, 31,32 thereby perpetuating a virus amplification response in the lung.…”

Section: Discussionmentioning

confidence: 57%

“…17 The access RT-PCR system (Promega, Madison, WI) was used as per the manufacturers' instructions. The reactions were carried out in a Perkin-Elmer DNA Thermal Cycler 480 with a temperature profile of 48°C for 45 minutes, one cycle; 94°C for 2 minutes, one cycle; 94°C for 30 seconds, 60°C for 1 minute, 68°C for 2 minutes, 25 cycles; 68°C for 7 minutes.…”

Section: Rt-pcr Analysis For Cxcl10 and Mcp-1mentioning

confidence: 99%

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Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Sui

Pinson

et al. 2005

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 57%

Section: Rt-pcr Analysis For Cxcl10 and Mcp-1mentioning

confidence: 99%

Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Sui

Pinson

et al. 2005

The American Journal of Pathology

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“…The eggs induced granulomas and a strong T helper type 2 (Th2) response. Macrophages comprising the granulomas developed highly productive infection with the virus (8). The dramatic effect of host factors on replication of the virus was identified in our subsequent studies.…”

Section: Pneumonia Is a Major Complication Of Human Immunodeficiency mentioning

confidence: 70%

“…The dramatic effect of host factors on replication of the virus was identified in our subsequent studies. In previous reports, we (26,33) have shown that monocyte chemotactic protein-1 (MCP-1), CXC chemokine ligand 10 (CXCL10), interleukin-4 (IL-4), and platelet-derived growth factor (PDGF) caused enhancement of viral replication in macrophages, and these cytokines were found in abundance in inflamed virus-infected lungs of macaques (8,11,33).…”

Section: Pneumonia Is a Major Complication Of Human Immunodeficiency mentioning

confidence: 99%

Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques

Dhillon¹,

Pinson²,

Dhillon³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pneumonia is a major complication of human immunodeficiency virus (HIV) pathogenesis but it develops only after prolonged infection. We used the macaque model to explore a hypothesis that the disease is a two-stage process, the first stage being establishment of the viral infection in the lung and the second being amplification of virus replication by host factors induced by chemical agents or opportunistic pathogens in the lung. Bleomycin, a chemical known to induce diffuse alveolar damage and pulmonary fibrosis with accumulation of macrophages and a rich T helper type 2 (Th2) cytokine environment, was inoculated intratracheally into five of eight SHIV 89.6P-infected macaques and into one uninfected macaque. Three additional simian HIV (SHIV)-infected macaques without bleomycin treatment served as untreated virus controls. Although none of the animals became clinically ill, bleomycin induced classical host responses in the lungs of all the treated, virus-infected macaques. There was enhanced production of the chemokine, monocyte chemotactic protein-1 (MCP-1), that had previously been shown to cause enhanced replication of the virus. Four of the five treated animals developed more productive SHIV infection in the lungs compared with the infected untreated animals. Enhanced virus replication was found primarily in infiltrating macrophages. Enhanced replication of the virus in the lungs was associated with host factors induced by the drug and supported the hypothesis for a two-stage process of pulmonary pathogenesis.

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“…In the same study, we also showed that macrophages in Freund adjuvant-induced granulomas that were rich in IFN-␥ were poorly permissive for virus replication. 18 These data clearly suggested that IL-4 was critical for promoting X4 virus replication. In the present report, we explored the concept of whether antisense (AS) DNA of IL-4 could inhibit replication of pathogenic SHIV in cultures of macaque CD4 ϩ T cells and macrophages and, importantly, in macaques infected with this virus.…”

Section: Introductionmentioning

confidence: 87%

Inhibition of pathogenic SHIV replication in macaques treated with antisense DNA of interleukin-4

Dhillon

Sui

Potula

et al. 2005

Blood

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IntroductionThe pathogenesis of HIV infection and the complex disease patterns caused by the virus are known to revolve around the dystrophic effects of the infection first, in helper CD4 ϩ T cells, and later in cells of the macrophage lineage in organs such as the lungs, spleen, and brain. [1][2][3][4][5][6] Loss of virus-infected CD4 ϩ T cells heralds the loss of interferon-␥ (IFN-␥)-mediated T-cell responses, and this creates an environment favorable for productive replication of opportunistic pathogens. Some of these agents are powerful inducers of T helper 2 (Th2) immune responses. 7,8 Studies on coreceptor usage of HIV have shown that viruses that use the CCR5 (R5) coreceptor are usually associated with virus invasion across mucosal surfaces and highly productive phase of virus replication in activated memory CD4 ϩ T lymphocytes. In many infected individuals, mutant virus strains that use the CXCR4 (X4) coreceptor evolve following the loss of Th1 cellular immune responses. Most of these viruses are capable of replicating only in naive CD4 ϩ T lymphocytes, including T-cell lines, 9,10 but some are also known to be dual tropic and capable of replicating productively in macrophages. 11,12 Studies on replication of X4 HIV-1 in human macrophage cultures showed that interleukin-4 (IL-4) caused significant enhancement of virus replication. 13 Whether IL-4 induced by opportunistic pathogens in immunocompromised HIV-infected persons causes enhancement of X4 virus replication is not known.We have used the macaque simian-human immunodeficiency virus (SHIV) model of HIV disease to study the role of macrophagetropic X4 viruses in the pathogenesis of AIDS and neurologic disease and, in particular, the interaction between the virus and macaque macrophages. Pathogenic SHIVs that have the X4 env gene of HIV-1 in a background of SIV mac 239 such as SHIV 89.6 P 14 and SHIV KU 15 cause acute loss of naive CD4 ϩ T cells, AIDS, and neurologic disease in macaques. 11 In earlier reports, we had shown that neuropathologic effects by these viruses were associated with expression of IL-4 in the brain, 16 supporting the findings of Gabuzda and Sobel 17 that X4 viruses replicating in brain macrophages can cause neurologic disease and of Valentin et al, 13 who showed that IL-4 promoted HIV replication in human macrophages. In a subsequent study, we used SHIV-infected macaques to determine whether opportunistic pathogens that induce IL-4 could promote replication of the virus in tissue macrophages of these animals. We injected Schistosoma mansoni eggs, potent inducers of Th2 cytokines, into the portal vein or intratracheally into SHIVinfected macaques. This resulted in the development of granulomas in the liver and lung in a milieu rich in IL-4. Macrophages comprising the granulomas were shown to be productively infected with the virus. In the same study, we also showed that macrophages in Freund adjuvant-induced granulomas that were rich in IFN-␥ were poorly permissive for virus replication. 18 These data clearly suggested that IL-4 wa...

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INHIBITORY AND ENHANCING EFFECTS OF IFN-γ AND IL-4 ON SHIVKUREPLICATION IN RHESUS MACAQUE MACROPHAGES: CORRELATION BETWEEN TH2CYTOKINES AND PRODUCTIVE INFECTION IN TISSUE MACROPHAGES DURING LATE-STAGE INFECTION

Cited by 24 publications

References 33 publications

Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques

Inhibition of pathogenic SHIV replication in macaques treated with antisense DNA of interleukin-4

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