Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

Slyker, Jennifer A.; Rowland‐Jones, Sarah; Dong, Tao; Reilly, Marie; Richardson, Barbra A.; Emery, Vincent C.; Atzberger, Ann; Mbori‐Ngacha, Dorothy; Lohman-Payne, Barbara; John‐Stewart, Grace

doi:10.1128/jvi.00790-12

Cited by 29 publications

(25 citation statements)

References 34 publications

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“…In addition, detection of CMV DNA in Kenyan infants (both infected and noninfected with HIV) was shown to be correlated with the increased frequency of activated and apoptosis vulnerable CD4 and CD8 cells; the increase was more pronounced in the HIV‐infected infants . CMV detection was associated with the level of activated CD4 positive cells, and the CMV viral load with the level of activated CD8 positive cells.…”

Section: Resultsmentioning

confidence: 94%

“…The lymphocytes are the primary target cells for HIV replication, and accumulation of these may increase the risk of transmission . There are also speculations that there are synergistic mechanisms on CD4 positive T‐lymphocyte activation between the 2 immunosuppressive viruses …”

Section: Discussionmentioning

confidence: 99%

“…Although the number of studies is limited, they all report similar findings. In Kenya, Slyker et al found both increased progression and mortality among HIV‐infected infants and increased mortality in their CMV coinfected mothers. CMV viremia has also been shown to be an independent risk factor for death in Tanzania, South Africa, and Zimbabwe .…”

Section: Discussionmentioning

confidence: 99%

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Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

et al. 2016

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Section: Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

et al. 2016

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“…The median viability of thawed PBMCs during this time was 72.4% (interquartile range 60.0–80.5%). As previously described, cells were stained with panels of antibodies to identify activated and apoptosis-vulnerable T cells (Slyker et al, 2011, 2012). Cells were thawed in FCS, washed twice with PBS plus 0.5% BSA and 0.5 mM EDTA (PBE), and stained with CD3-Pacific Blue (UCHT1, Dakocytomation, Angel Drove, UK), CD4-APC-Cy7 (RPA-T4, BD Pharmingen, Oxford, UK), CD8-PE-Cy7 (RPA-T8, Pharmingen), CD56-PE-Cy5 (N901 (NKH-1), Beckman Coulter, High Wycombe, UK), CD16-APC-Cy7 (3G8, Pharmingen), CD69-FITC (FN50, Dakocytomation), CD38-PE (AT13/5, Serotec, Oxford, UK), HLA-DR-APC (TU36, Pharmingen), CD57-FITC (TB01, Serotec), CD71-APC (M-A712, Pharmingen), CD95-APC (DX2, Pharmingen), Bcl-2-FITC (124, Dakocytomation), Perforin-PE (27-35, Pharmingen), CD27-APC (0323, eBioscience, San Diego, CA, USA), CD28-FITC (CD28.1, Dakocytomation), CCR7-PE (FAB197, R&D Systems, Minneapolis, MN, USA) and CD45RA-APC (HI-100, Pharmingen).…”

Section: Methodsmentioning

confidence: 99%

The impact of HIV-1 infection and exposure on natural killer (NK) cell phenotype in Kenyan infants during the first year of life

Slyker¹,

Lohman-Payne²,

John‐Stewart³

et al. 2012

Front. Immun.

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Natural killer (NK) cells play an important role in the containment of HIV replication during primary infection, though their functions are impaired during chronic HIV infection. Infants experience more rapid HIV disease progression than adults, but contributions of infant NK cells to containing HIV infection are unknown. The aim of this study was to determine the impact of HIV infection on infant NK cell phenotype by evaluating samples and data from a cohort study of women and their infants, conducted in Nairobi, Kenya between 1999 and 2003. The percentage and phenotype of NK cells was evaluated longitudinally by multi-parameter flow cytometry over the first year of life in HIV-infected (HIV+, = 16), HIV-exposed uninfected (HIV-EU, n = 6), and healthy unexposed controls (HIV–, n = 4). At birth, NK subset distributions based on expression of CD56 and CD16 did not differ between HIV+, HIV-EU, or HIV– infants. However, HIV infection was associated with a subsequent decline in NK cells as a percentage of total lymphocytes (p < 0.001), and an expanding proportion of CD56-CD16+ NK cells (p < 0.001). Activated CD38brightCD69+ NK cells were more frequent in the HIV+ infants, followed by HIV-EU and HIV- infants, in both CD56dim (p = 0.005) and CD56bright compartments (p = 0.03). HIV infection and exposure was also associated with a significant decline in the percentage of perforin-expressing NK cells in the CD56dim compartment over the first year of life, with HIV+ infants losing approximately 2.5% (p < 0.001) and HIV-EU infants losing 3.0% (p = 0.01) of perforin+ cells per month. Thus, infant HIV infection is associated with alterations in NK cell subsets, activation, and cytolytic potential that could contribute to their poor control over HIV infection. Furthermore, exposure to HIV infection in infants who escaped infection is also associated with alterations in NK cells that may contribute to the reduced ability to fight infections that is observed in HIV-EU infants.

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“…Congenital disease can be a source of considerable morbidity, whereas postpartum infection is typically asymptomatic in healthy, full-term infants [9]. However, in resource-limited settings, CMV has been suggested as a cause for morbidity and decreased growth in infants of HIV-infected mothers, even in HIV-uninfected infants [10, 11]. Additionally, symptomatic perinatal CMV infections have been described in infants exposed to but uninfected with HIV (hereafter, “HIV-exposed-uninfected infants”) [12].…”

mentioning

confidence: 99%

Cytomegalovirus Infection in Human Immunodeficiency Virus (HIV)–Exposed and HIV-Infected Infants: A Systematic Review

2015

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Cytomegalovirus is highly prevalent worldwide and an important opportunistic pathogen in human immunodeficiency virus (HIV)–infected individuals. The effects of cytomegalovirus infection on HIV-exposed infants are poorly understood. We conducted a systematic review to assess the relationship between cytomegalovirus and HIV infections among HIV-exposed infants. Limited evidence suggests that HIV-induced immunosuppression in the mother increases the rate of congenital cytomegalovirus infection, while maternal antiretroviral therapy may reduce it. Limited information exists on the direction of the relationship between cytomegalovirus and HIV transmission among HIV-exposed infants. Only 2 studies have addressed this temporal sequence of events, and they suggest that cytomegalovirus can lead to subsequent HIV infection in HIV-exposed infants. Most evidence suggests that early cytomegalo-virus infection accelerates HIV disease progression in infants. Gaps remain in understanding the role that cytomegalovirus infection plays in HIV-exposed infants. Decreasing cytomegalovirus transmission prenatally and in infancy might further decrease HIV transmission and lead to better health among HIV-exposed infants.

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Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

Cited by 29 publications

References 34 publications

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

The impact of HIV-1 infection and exposure on natural killer (NK) cell phenotype in Kenyan infants during the first year of life

Cytomegalovirus Infection in Human Immunodeficiency Virus (HIV)–Exposed and HIV-Infected Infants: A Systematic Review

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