VEGF Polymorphism rs3025039 and Human T-Cell Leukemia Virus 1 (HTLV-1) Infection among Older Japanese Individuals: A Cross-Sectional Study

Shimizu, Yūji; Yamanashi, Hirotomo; Miyata, Jun; Takada, M.; Noguchi, Yuko; Honda, Yukiko; Nonaka, Fumiaki; Nakamichi, Seiko; Nagata, Yasunobu; Maeda, Takahiro

doi:10.3390/bioengineering9100527

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…In addition, in our previous study, genetic characteristics related to lower angiogenesis activity were revealed to be associated with a lower chance of establishing HTLV-1 infection [60]. Therefore, individuals with HTLV-1 infection might have higher angiogenesis activity than individuals without HTLV-1 infection, which prevents hypertension.…”

Section: Human T-cell Leukemia Virus Type 1 (Htlv-1) Structural Ather...mentioning

confidence: 88%

Progression of Carotid Intima-Media Thickness Partly Indicates the Prevention of Hypertension among Older Individuals in the General Population

Shimizu

2023

Life

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Structural atherosclerosis, as evaluated by carotid intima-media thickness (CIMT), is reported to be positively associated with hypertension. However, angiogenesis, which plays an important role in the progression of structural atherosclerosis, prevents hypertension by reducing peripheral vascular resistance. These associations evoke a contradiction: characteristics associated with the progression of structural atherosclerosis, which is related to hypertension, might prevent hypertension. To clarify novel mechanisms underlying the association between structural atherosclerosis and hypertension, multifaceted analyses are necessary. We performed several epidemiological studies based on this concept. This study summarizes those epidemiological studies and adds some discussion. Studies focusing on circulating CD34-positive cells, single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF), SNPs in BRACA1-associated protein (BRAP), platelets, human T-cell leukemia virus type 1 (HTLV-1), and SNPs in aldehyde dehydrogenase 2 (ALDH2) have shown that active endothelial repair, which leads to the progression of structural atherosclerosis, helps prevent hypertension. These associations indicate that the progression of structural atherosclerosis could act as a marker of angiogenesis, which reduces peripheral vascular resistance. In general, a positive association between structural atherosclerosis and hypertension has been reported. However, the progression of structural atherosclerosis could act as a marker of activity that prevents hypertension via reductions in peripheral vascular resistance.

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Section: Human T-cell Leukemia Virus Type 1 (Htlv-1) Structural Ather...mentioning

confidence: 88%

Progression of Carotid Intima-Media Thickness Partly Indicates the Prevention of Hypertension among Older Individuals in the General Population

Shimizu

2023

Life

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“…Since 1990, much has been discussed about the relationship between genotypes and HTLV-1 disease progression ( 51 ). Until recent years many polymorphisms had been described as related to the progression of HTLV-1infection including human leucocyte antigen (HLA) genes ( 52 ), the immunoregulation-related gene FOXP3 ( 53 ), the vascular endothelial growth factor (VEGF) gene ( 54 ), Tax-responsive elements (TRE) gene ( 55 ), Mannose-binding lectin-associated serine protease 2 (MASP2) gene ( 56 ) and others that could be related to the pro-viral load control or development of clinical manifestations including HAM/TSP. In our in vitro model, the ACs, HAM/TSP, and ATLL patients donated only IgG antibodies, indicating that genetic factors related to any molecules other than the genes related to donnor’s IgG production could not influence the observed results.…”

Section: Discussionmentioning

confidence: 99%

Differential modulation of IL-4, IL-10, IL-17, and IFN-γ production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and γδ) and B cells

Machado,

Fagundes,

Fernandes

et al. 2023

Front. Med.

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Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-γ-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-γ-producing γδT cells without influence on IL-17- and IL4-producing γδT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-γ producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.

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“…However, despite the large number of HTLV-1 carriers worldwide, the safety of aflibercept for patients infected with HTLV-1 has not been explored in basic ophthalmologic studies. Numerous studies have demonstrated a relationship between HTLV-1 infection and VEGF (63)(64)(65)(66), which is a key factor in the pathogenesis of HU (67). One study reported the development of corneal endotheliitis in a patient infected with human herpesvirus-6 (HHV-6) after intravitreal injection of an anti-VEGF antibody (68).…”

Section: Discussionmentioning

confidence: 99%

Safety of intraocular anti-VEGF antibody treatment under in vitro HTLV-1 infection

et al. 2023

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IntroductionHTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1–associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti–vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF165, the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro.MethodsWe used MT2 and TL-Om1 cells as HTLV-1–infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1–infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments.ResultsAnti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1–infected T cells.ConclusionThis preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1–related inflammation and thus may be safe for use.

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VEGF Polymorphism rs3025039 and Human T-Cell Leukemia Virus 1 (HTLV-1) Infection among Older Japanese Individuals: A Cross-Sectional Study

Cited by 5 publications

References 24 publications

Progression of Carotid Intima-Media Thickness Partly Indicates the Prevention of Hypertension among Older Individuals in the General Population

Progression of Carotid Intima-Media Thickness Partly Indicates the Prevention of Hypertension among Older Individuals in the General Population

Differential modulation of IL-4, IL-10, IL-17, and IFN-γ production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and γδ) and B cells

Safety of intraocular anti-VEGF antibody treatment under in vitro HTLV-1 infection

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