<i>nef</i>
            Gene Is Required for Robust Productive Infection by Simian Immunodeficiency Virus of T-Cell-Rich Paracortex in Lymph Nodes

Sugimoto, Chie; Tadakuma, Kei; Otani, Isao; Moritoyo, Takashi; Akari, Hirofumi; Ono, Fumiko; Yoshikawa, Yasuhiro; Sata, Tetsutaro; Izumo, Shuji; Mori, Kazuyasu

doi:10.1128/jvi.77.7.4169-4180.2003

Cited by 26 publications

(28 citation statements)

References 57 publications

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“…Nef is suggested to contribute to this phenomenon by impairing antigen presentation and prevention of B-cell class switching following transfer from infected cells (40)(41)(42)(43). The results presented herein, in line with those from other laboratories (44,45), suggest that Nef also suppresses B-cell help by HIV-1-infected T lymphocytes. In addition, the observed reduction of parenchymal lymphocyte motility may facilitate cell-associated virus spread in the context of HIV-1 infection.…”

Section: Discussionsupporting

confidence: 81%

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

Stolp

Imle

Coelho

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef’s influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef’s ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor.

show abstract

Section: Discussionsupporting

confidence: 81%

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

Stolp

Imle

Coelho

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…ϩ T cells in the B cell region of the LN, where follicular helper CD4 ϩ T cells reside, but not in the T cell region, where CM, TrM, and naive CD4 ϩ T cells reside (51). Thus, SIV⌬5G shares an in vivo property with SIV⌬nef.…”

Section: Discussionmentioning

confidence: 94%

“…Our study demonstrates that a 1-to 2-log lower acute viral load among the CD4 ϩ T cells in SLT occurs during "nonpathogenic" ⌬5G-infected animals compared to SIVmac239-infected animals. In addition, such lower levels of infection in the ⌬5G-infected animals are associated with the preservation of CXCR3 ϩ CCR5 ϩ TrM CD4 ϩ T cells, i.e., TrM-Th1 cells whose depletion is linked to an insufficient virusspecific cellular response leading to persistent viral replication in SIVmac239 infection (28,51).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Glycosylation of Simian Immunodeficiency Virus Influences Immune-Tissue Targeting during Primary Infection, Leading to Immunodeficiency or Viral Control

Sugimoto

Nakamura

Hagen

et al. 2012

J Virol

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Glycans of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) play pivotal roles in modulating virus-target cell interactions. We have previously reported that, whereas SIVmac239 is pathogenic, its deglycosylated essentially nonpathogenic mutant (Δ5G) serves as a live-attenuated vaccine, although both replicate similarly during primary infection. These findings prompted us to determine whether such a polarized clinical outcome was due to differences in the immune tissues targeted by these viruses, where functionally and phenotypically different memory CD4 + T cells reside. The results showed that Δ5G replicates in secondary lymphoid tissue (SLT) at 1- to 2-log-lower levels than SIVmac239, whereas SIVmac239-infected but not Δ5G-infected animals deplete CXCR3 + CCR5 + transitional memory (TrM) CD4 + T cells. An early robust Δ5G replication was localized to small intestinal tissue, especially the lamina propria (effector site) rather than isolated lymphoid follicles (inductive site) and was associated with the induction and depletion of CCR6 + CXCR3 − CCR5 + effector memory CD4 + T cells. These results suggest that differential glycosylation of Env dictates the type of tissue-resident CD4 + T cells that are targeted, which leads to pathogenic infection of TrM-Th1 cells in SLT and nonpathogenic infection of Th17 cells in the small intestine, respectively.

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“…Nef is a protein that is unique to simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) and is not found in other viruses (40). The importance of this protein in pathogenesis is clear from the striking attenuation of SIVand HIV-1-induced disease in macaques and humans when Nef is defective (9,11,12,13,18,26).…”

mentioning

confidence: 99%

Predicting the Impact of Blocking Human Immunodeficiency Virus Type 1 Nef In Vivo

Wick

Gilbert

Yang

2009

J Virol

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nef Gene Is Required for Robust Productive Infection by Simian Immunodeficiency Virus of T-Cell-Rich Paracortex in Lymph Nodes

Cited by 26 publications

References 57 publications

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

Glycosylation of Simian Immunodeficiency Virus Influences Immune-Tissue Targeting during Primary Infection, Leading to Immunodeficiency or Viral Control

Predicting the Impact of Blocking Human Immunodeficiency Virus Type 1 Nef In Vivo

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