Browsing by Author "Eller, Leigh Anne"

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    Elevated Natural Killer Cell Activity Despite Altered Functional and Phenotypic Profile in Ugandans With HIV-1 Clade A or Clade D Infection
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2009) Eller, Michael A.; Eller, Leigh Anne; Ouma, Benson J.; Thelian, Doris; Gonzalez, Veronica D.; Guwatudde, David; McCutchan, Francine E.; Marovich, Mary A.; Michael, Nelson L.; Souza, Mark S. de; Wabwire-Mangen, Fred; Robb, Merlin L.; Currier, Jeffrey R.; Sandberg, Johan K.
    Natural killer (NK) cells most likely contribute toward limiting HIV-1 replication, and investigation into their function throughout the course of infection is therefore important. We here aimed to determine the state of the NK cell compartment in Ugandans with untreated HIV-1 clade A or D infection in comparison with matched uninfected controls. Methods and Results: The function and phenotype of NK cells were investigated using 10-color flow cytometry. Surprisingly, NK cells displayed elevated production of interferon-g and macrophage inflammatory protein 1b, as well as CD107a degranulation in infected subjects. This included unexpected levels of degranulation in the CD56bright subset of NK cells and high levels of macrophage inflammatory protein 1b in CD56negative NK cells. HIV-1 infection was associated with reduced expression of KIR2DL1, NKG2A, CD161, and NKp30 in CD56dim and CD56negative NK cells, whereas lowered CD161 expression was the only alteration in the CD56bright subset. Interestingly, low CD4 counts were associated with increased levels of interferon-g and degranulation in CD56bright NK cells, as well as increased NKp44 expression in the CD56dim cells. NK cells in HIV-1–infected Ugandans display elevated activity, despite an altered functional and phenotypic profile. Furthermore, specific alterations in the CD56bright and CD56dim subsets occur in patients with severe CD4 loss.
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    Relatively Low HIV Infection Rates in Rural Uganda, but with High Potential for a Rise: A Cohort Study in Kayunga District, Uganda
    (PLoS ONE, 2009) Guwatudde, David; Wabwire-Mangen, Fred; Eller, Leigh Anne; Eller, Michael; McCutchan, Francine; Kibuuka, Hannah; Millard, Monica; Sewankambo, Nelson; Serwadda, David; Michael, Nelson; Robb, Merlin
    Few studies have been conducted in Uganda to identify and quantify the determinants of HIV-1 infection. We report results from a community-based cohort study, whose primary objectives were to determine HIV-1 prevalence, incidence, and determinants of these infections, among other objectives. Methodology: Consenting volunteers from the rural district of Kayunga in Uganda aged 15–49 years were enrolled between March and July 2006. Participants were evaluated every six months. A questionnaire that collected information on behavioral and other HIV-1 risk factors was administered, and a blood sample obtained for laboratory analysis at each study visit. Principal Findings: HIV-1 prevalence among the 2025 participants was 9.9% (95% CI = 8.6%–11.2%). By the end of 12 months of follow-up, 1689.7 person-years had been accumulated, with a median follow-up time of 11.97 months. Thirteen HIV-1 incident cases were detected giving an annual HIV-1 incidence of 0.77% (95% CI = 0.35–1.19). Prevalence of HSV-2 infection was 57% and was strongly associated with prevalent HIV-1 infection (adjusted Odds Ratio = 3.9, 95% CI = 2.50–6.17); as well as incident HIV-1 infection (adjusted Rate Ratio (RR) = 8.7, 95% CI = 1.11–67.2). The single most important behavioral characteristic associated with incident HIV infection was the number of times in the past 6 months, a participant had sex with person(s) they suspected/knew were having sex with others; attaining statistical significance at 10 times and higher (adjusted RR = 6.3, 95% CI = 1.73–23.1). By the end of 12 months of follow-up, 259 participants (13%) were lost to follow-up, 13 (0.6%) had died, and 2 (0.1%) had withdrawn consent. Conclusions: Despite relatively low HIV-1 incidence observed in this community, prevalence remains relatively high. In the presence of high prevalence of HSV-2 infection and the behavioral characteristic of having sex with more than one partner, there is potential for increase in HIV-1 incidence.
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    Short Communication Colony-Forming Hematopoietic Progenitor Cells Are Not Preferentially Infected by HIV Type 1 Subtypes A and D in Vivo
    (AIDS research and human retroviruses, 2012) Mullis, Caroline E.; Oliver, Amy E.; Eller, Leigh Anne; Guwatudde, David; Mueller, Amy C.; Eller, Michael A.; Kibuuka, Hannah; Robb, Merlin; Quinn, Thomas C.; Redd, Andrew D.
    HIV subtype C has previously been shown to infect hematopoietic progenitor cells (HPCs) at a significantly higher rate than subtype B. To better understand the subtype-specific nature of HPC infection, we examined the prevalence of HPC infection in vivo by HIV-1 subtypes A and D. HIV-1 infection of HPC was examined in 40 individuals, 19 infected with subtype A and 21 with subtype D, using a single colony assay format. DNA from 1177 extracted colonies was tested for integrated viral DNA of the p24 gene. Four colonies were found to be stably infected, three of 462 colonies (0.65%) from HIV-1A-infected individuals (1/19 individuals) and one of 715 colonies (0.14%) from HIV-1D-infected individuals (1/22 individuals). These rates of colony infection were comparable to the rates observed in PBMCs from the same subjects. Additionally, no correlation was observed between cell colony density and circulating viral load or proviral load. Our findings suggest that HIV-1 subtypes A and D do not preferentially infect colony-forming HPCs over mature HIV target cells in vivo.
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    Single-Cell Level Response of HIV-Specific and Cytomegalovirus-Specific CD4 T Cells Correlate With Viral Control in Chronic HIV-1 Subtype A Infection
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012) Eller, Michael A.; Eller, Leigh Anne; Ratto-Kim, Silvia; Ouma, Benson J.; Lo, Vicky; Souza, Mark de; Guwatudde, David; Nails, Barbara; Michael, Nelson L.; Wabwire-Mangen, Fred; Robb, Merlin L.; Marovich, Mary A.; Sandberg, Johan K.; Currier, Jeffrey R.
    HIV-1 subtype A is the second most prevalent subtype globally and is associated with reduced viral load, higher CD4 absolute counts, and slower disease progression. To study the possible role of T cells associated with better outcome, we examined CD4 and CD8 T-cell responses against HIV-1 and cytomegalovirus (CMV) in Ugandans infected with subtype A HIV-1. Methods: T-cell responses were investigated using flow cytometry and novel subtype A variant inclusive peptide (VIP) sets designed for this evaluation. CD4 T-cell responses focused primarily on Gag, whereas CD8 T-cell responses were broadly directed against Gag, gp41, and Nef VIP sets. CD4 T cells primarily responded with interferon (IFN)-g, whereas CD8 cells were more diverse with degranulation (CD107a), IFN-g, and macrophage inflammatory protein (MIP)-1b production. Results: No relationship was observed between CD8 T-cell responses and the HIV-1 load. Similarly, the frequency of CD4 T cells responding to these antigens did not associate with viral control. However, in CD4 T cells responding against Gag or CMV, the IFN-g intensity, indicative of the production at the singlecell level, was inversely proportional to viral load. No significant relationship was found between T-cell effector/memory phenotype and viral control. Conclusions: The per cell production of IFN-g in CD4 T cells responding to HIV-1 or CMV correlated with viral control in chronic HIV-1 subtype A infection. These data suggest that quantitative aspects at the single-cell level may be more important than the frequency of antigen-specific CD4 T cells in HIV-1 subtype A infection control.