Integrin α4β7 Is Downregulated on the Surfaces of Simian Immunodeficiency Virus SIVmac239-Infected Cells

Budde, Melisa L.; Lhost, Jennifer J.; Dudley, Dawn M.; Rakasz, Eva G.; O’Connor, David H.

doi:10.1128/jvi.00430-10

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…14 In addition, downregulation of α4β7 on the surface of SIV-infected cells may be important in CD4 depletion of the mucosal-associated lymphoid compartments and susceptibility to superinfection and/or immune evasion. 15 Depletion of CD4 from the gut is immune dysregulation in patients with HIV because of microbial translocation leading to chronic immune activation and an increase in proinflammatory cytokines. This state of immune activation persists even after treatment with antiretrovirals.…”

Section: Discussionmentioning

confidence: 99%

Treatment-Naïve HIV-Infected Patients Have Fewer Gut-Homing β7 Memory CD4 T Cells than Healthy Controls

Fadul

Couturier

et al. 2017

Southern Medical Journal

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Objectives The integrin α4β7 is the gut-homing receptor for lymphocytes. It also is an important co-receptor for human immunodeficiency virus (HIV) via glycoprotein (gp)120 binding. Depletion of gut cluster of differentiation (CD)4 T cells is linked to chronic inflammation in patients with HIV; however, measuring CD4 cells in the gut is invasive and not routine. As such, establishing a peripheral marker for CD4 depletion of the gut is needed. We hypothesized that α4β7 CD4 T cells are depleted in the peripheral blood of treatment-naïve patients with HIV compared with healthy controls. Methods The study groups were treatment-naïve patients with HIV and uninfected controls. Subjects were included if they were 18 years or older with no history of opportunistic infections, active tuberculosis, or cancer. We collected peripheral blood and examined on whole blood using flow cytometry for the following cell surface markers: CD4, CD45RO, chemokine receptor type 5, C-X-C chemokine receptor type 4 (CXCR4), and the integrin β7. We collected demographic information, including age, sex, and ethnicity, as well as viral load (VL) and CD4 count. Two-sample t tests and Fisher exact tests were used to compare the differences between the two groups. Spearman correlation coefficients were calculated between CD4 count and log10− VL and percentage of CD4+/CD45RO+/β7+ and log10− VL in patients. Results Twenty-two subjects were enrolled in the study (12 patients with HIV and 10 controls). There were no differences in age or sex between the two groups. There were more Hispanics and fewer Asians in the group comprising patients with HIV compared with the control group (7 vs 2 and 0 vs 4, P = 0.05, respectively). Patients infected with HIV had significantly lower frequencies of CD4+/CD45RO+/β7+ cells (median 12%, range 5–18 compared with uninfected controls: median 20%, range 11–26, P = 0.0007). There was a statistically significant difference in the percentage of CD4+/CD45RO+/C-X-C chemokine receptor type 4+ cells between patients (72%, range 60%–91%) compared with controls (79%, range 72%–94%, P = 0.04). The percentage of CD4+/CD45RO+/chemokine receptor type 5+ did not differ between the group of patients with HIV and the control groups (22%, range 11%–57% vs 27%, range 14%–31%; P = 0.8, respectively). There was no correlation between percentage of CD4+/CD45RO+/β+ cells and log10− VL as measured by the Spearman correlation coefficient (r = 0.05, P = 0.88) in patients infected with HIV. Conclusions Memory CD4 β7+ cells are reduced significantly in the peripheral blood of untreated patients infected with HIV, which could be used as a noninvasive indicator of intestinal CD4 T cell loss and recovery. Further studies are needed to examine whether depletion of these CD4+/CD45RO+/β7+ cells in the peripheral blood parallels depletion in the gut of treatment-naïve patients with HIV and whether levels return to control levels after treatment.

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Section: Discussionmentioning

confidence: 99%

Treatment-Naïve HIV-Infected Patients Have Fewer Gut-Homing β7 Memory CD4 T Cells than Healthy Controls

Fadul

Couturier

et al. 2017

Southern Medical Journal

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“…As one of the goals of any virus is to evade immune control (67), integrins may also be a worthwhile target. They can communicate with the cellular environment and engage multiple receptors, including immune receptors (15). Several viruses, including HIV, Ebola virus, simian immunodeficiency virus, HCMV, and Epstein-Barr virus (EBV), were shown to induce downregulation of surface integrins as part of their immune evasion strategy.…”

Section: Discussionmentioning

confidence: 99%

“…Several viruses, including HIV, Ebola virus, simian immunodeficiency virus, HCMV, and Epstein-Barr virus (EBV), were shown to induce downregulation of surface integrins as part of their immune evasion strategy. Modulation of cell surface integrin can influence lymphocyte trafficking, thereby protecting the cell from superinfection and facilitating virus release (15,31,71,86).…”

Section: Discussionmentioning

confidence: 99%

Equine Herpesvirus Type 4 UL56 and UL49.5 Proteins Downregulate Cell Surface Major Histocompatibility Complex Class I Expression Independently of Each Other

Said

Azab

Damiani

et al. 2012

J Virol

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“…With two RGD (arginine-glycine-aspartic acid) and 12 CSPG (chondroitin sulfate proteoglycan) domains, FREM1 variants can potentially exert different functions by differentially interacting with integrin, collagen, and fibronectin through variations in functional domains (26). These are important components of the genital mucosal barrier and play an important role in HIV-1 infection (4,6,7,10,13,14,33,43,51). The C-type lectin and Calx-beta domain of FREM1 suggest the ability of this protein to bind sugar and calcium and modify biological function.…”

Section: Discussionmentioning

confidence: 99%

A Genetic Polymorphism of FREM1 Is Associated with Resistance against HIV Infection in the Pumwani Sex Worker Cohort

Luo

Sainsbury

Tuff

et al. 2012

J Virol

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A subgroup of women enrolled in the Pumwani sex worker cohort remain seronegative and PCR negative for human immunodeficiency virus type 1 despite repeated exposure through high-risk sex work. Studies have shown that polymorphisms of genes involved in antigen presentation and viral restriction factors are associated with resistance to HIV infection. To discover other possible genetic factors underlying this HIV-resistant phenotype, we conducted an exploratory nonbiased, low-resolution, genome-wide single-nucleotide polymorphism (SNP) analysis comparing 60 HIV-resistant women to 48 HIV-infected controls. The SNP minor allele rs1552896, in an intron of FREM1, was significantly associated with the resistant phenotype (P ‫؍‬ 1.68 ؋ 10 ؊5 ; adjusted P ‫؍‬ 2.37 ؋ 10 ؊4 ; odds ratio [OR], 9.51; 95% confidence interval [CI], 2.82 to 32.05). We expanded the sample size by genotyping rs1552896 in the Pumwani cohort and comparing 114 HIV-resistant women to 609 HIV-infected controls and confirmed the association (P ‫؍‬ 1.7 ؋ 10 ؊4 ; OR, 2.67; 95% CI, 1.47 to 4.84). To validate the association in a second cohort, we genotyped 783 women enrolled in a mother-child health study and observed the minor allele of rs1552896 enriched in HIV-uninfected women (n ‫؍‬ 488) compared to HIV-infected enrollees (n ‫؍‬ 295) (P ‫؍‬ 0.036; OR, 1.69; 95% CI, 0.98 to 2.93). Quantitative reverse transcription-PCR showed that FREM1 mRNA was highly expressed in tissues relevant for HIV-1 infection, and immunohistochemical analysis revealed that FREM1 protein is expressed in the ectocervical mucosa of HIV-resistant women. The significant association of rs1552896 with an HIV-resistant phenotype, together with the expression profile of FREM1 in tissues relevant to HIV infection, suggests that FREM1 is a potentially novel candidate gene for resistance to HIV infection.

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Integrin α4β7 Is Downregulated on the Surfaces of Simian Immunodeficiency Virus SIVmac239-Infected Cells

Cited by 9 publications

References 42 publications

Treatment-Naïve HIV-Infected Patients Have Fewer Gut-Homing β7 Memory CD4 T Cells than Healthy Controls

Treatment-Naïve HIV-Infected Patients Have Fewer Gut-Homing β7 Memory CD4 T Cells than Healthy Controls

Equine Herpesvirus Type 4 UL56 and UL49.5 Proteins Downregulate Cell Surface Major Histocompatibility Complex Class I Expression Independently of Each Other

A Genetic Polymorphism of FREM1 Is Associated with Resistance against HIV Infection in the Pumwani Sex Worker Cohort

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