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Sylwester, Andrew; Mitchell, Bridget L.; Edgar, John B.; Taormina, Cara; Pelte, Christian; Ruchti, Franziska; Sleath, Paul R.; Grabstein, Kenneth H.; Hosken, Nancy; Kern, Florian; Nelson, Jay A.; Picker, Louis J.

doi:10.1084/jem.20050882101805c

Cited by 7 publications

(11 citation statements)

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“…This chronic activation may also be an important factor in maintaining the HIV reservoir (16). Along with HIV itself, CMV could be an important mediator of immune activation, especially because a large fraction of an infected person's immune repertoire is targeted toward CMV (40,41), and CMV reactivation in the genital tract is common, even in subjects with high CD4 ϩ T cell counts during ART (42). Similar to our previous reports on ART-naive HIV-infected men, we found that asymptomatic CMV replication in the male genital tract was associated with higher levels of systemic CD4 ϩ T cell activation and proliferation and also with higher levels of systemic CD4 ϩ T cell-associated provirus, even during suppressive ART.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 ⁺ T Cell Activation during Antiretroviral Treatment

Gianella

Massanella

Richman

et al. 2014

J Virol

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Asymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4 ؉ T cells in blood (P < 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4؉ T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P ‫؍‬ 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P ‫؍‬ 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4 ؉ (P < 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations. IMPORTANCEAlmost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in blood, and the size of the HIV DNA reservoir in 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. In support of our primary hypothesis, shedding of CMV DNA in semen was associated with increased activation and proliferation of T cells in blood and also significantly higher levels of HIV DNA in blood cells. These results suggest that CMV reactivation might play a role in the maintenance of the HIV DNA reservoir during suppressive ART and that it could be a target of pharmacologic intervention in future studies.

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Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 ⁺ T Cell Activation during Antiretroviral Treatment

Gianella

Massanella

Richman

et al. 2014

J Virol

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“…It is well known that HCMV can elicit lifelong high‐frequency CMV‐specific T‐cell responses . The average CD4 and CD8 T‐cell response is ∼10% of the total memory T‐cell compartment in peripheral blood, which makes HCMV possibly the most immunogenic microbe known for the human immune system.…”

Section: Impact Of CMV Infection On the T‐cell Immune Systemmentioning

confidence: 99%

“…In a systems‐analysis of twins discordant for HCMV, it was shown that HCMV has indeed a major non‐heritable impact on immune parameters such as effector CD8 T cells . However, the T‐cell responses vary greatly among HCMV‐infected individuals, ranging from 0.1‐40% . The high variability in response to CMV might be caused by differences in the initial viral inoculum and the immunocompetence of the host during infection .…”

Section: Impact Of CMV Infection On the T‐cell Immune Systemmentioning

confidence: 99%

5^th International Workshop on CMV and Immunosenescence ‐ A shadow of cytomegalovirus infection on immunological memory

et al. 2015

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“…In some cases, T cells responding to genes expressed under the immediate-early promotor may help provide checkpoints to limit viral replication (Simon et al, 2006). However, in general it has been difficult to link immunodominance with viral gene-expression patterns, especially in human CMVs (Sylwester et al, 2005), in which T cell responses to structural proteins that are not under the immediate-early promotor commonly dominate (Khan et al, 2002). Even in MCMV, the fact that only one of two epitopes from the same protein (M38) is inflationary suggests factors other than the kinetics of viral gene expression are involved (Munks et al, 2006).…”

mentioning

confidence: 99%

CMV and the Art of Memory Maintenance

Klenerman

Dunbar

2008

Immunity

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Cited by 7 publications

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Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 ⁺ T Cell Activation during Antiretroviral Treatment

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 ⁺ T Cell Activation during Antiretroviral Treatment

5^th International Workshop on CMV and Immunosenescence ‐ A shadow of cytomegalovirus infection on immunological memory

CMV and the Art of Memory Maintenance

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Cited by 7 publications

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Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 + T Cell Activation during Antiretroviral Treatment

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 + T Cell Activation during Antiretroviral Treatment

5th International Workshop on CMV and Immunosenescence ‐ A shadow of cytomegalovirus infection on immunological memory

CMV and the Art of Memory Maintenance

Contact Info

Product

Resources

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Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 ⁺ T Cell Activation during Antiretroviral Treatment

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4 ⁺ T Cell Activation during Antiretroviral Treatment

5^th International Workshop on CMV and Immunosenescence ‐ A shadow of cytomegalovirus infection on immunological memory