Transfusion‐transmitted cytomegalovirus (CMV) infections in a murine model: characterization of CMV‐infected donor mice

Roback, John D.; Su, Leon; Newman, James L.; Saakadze, Natia; Lezhava, Levan J.; Hillyer, Christopher D.

doi:10.1111/j.1537-2995.2006.00820.x

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…Horizontal transmission has also been demonstrated in mouse models of blood transfusion (Cheung and Lang, 1977; Roback et al, 2006). We employed a transfusion model to investigate whether PM-mediated MCMV dissemination is sufficient to promote systemic infection.…”

Section: Resultsmentioning

confidence: 97%

“…Further, macrophages are a major latent reservoir (Pollock et al, 1997), analogous to humans (Revello et al, 1998) but difficult to track in naturally infected immunocompetent adults. Regardless of immune status, cell-free virus is not produced in mice (Roback et al, 2006) or humans (Gilbert et al, 1989; Yeager et al, 1981). A blood mononuclear phagocyte transports MCMV (Stoddart et al, 1994), potentially acquiring virus from vascular endothelial cells at initial sites (Sacher et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Cytomegalovirus Hijacks CX3CR1hi Patrolling Monocytes as Immune-Privileged Vehicles for Dissemination in Mice

Daley‐Bauer

Roback

Wynn

et al. 2014

Cell Host & Microbe

111

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SUMMARY Peripheral blood myelomonocytic cells are important for cytomegalovirus dissemination to distal organs such as salivary glands where persistent replication and shedding dictates transmission patterns. We find that this process is markedly enhanced by the murine cytomegalovirus (MCMV)-encoded CC chemokine, MCK2, which promotes recruitment of CX3CR1hi patrolling monocytes to initial infection sites in the mouse. There, these cells become infected and traffic via the bloodstream to distal sites. In contrast, inflammatory monocytes, the other major myelomonocytic subset, remain virus negative. CX3CR1 deficiency prevents patrolling monocyte migration on the vascular endothelium and interrupts MCMV dissemination to the salivary glands independent of antiviral NK and T cell immune control. In this manner, CX3CR1hi patrolling monocytes serve as immune-privileged vehicles to transport MCMV via the bloodstream to distal organs. MCMV commandeers patrolling monocytes to mediate systemic infection and seed a persistent reservoir essential for horizontal transmission.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus Hijacks CX3CR1hi Patrolling Monocytes as Immune-Privileged Vehicles for Dissemination in Mice

Daley‐Bauer

Roback

Wynn

et al. 2014

Cell Host & Microbe

111

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“…Acute infection of HCMV often causes altered haematopoietic profiles, and latent infection of HSPCs can lead to graft failure, and to CMV transmission and infection in haematopoietic cell-transplant (HCT) recipients [2,41]. MCMV has been used extensively as a model to study the pathophysiology, latency and reactivation of CMV in vivo [20,21,42]. MCMV infection can cause haematologic abnormalities similar to HCMV [27].…”

Section: Discussionmentioning

confidence: 99%

A novel murine model of differentiation-mediated cytomegalovirus reactivation from latently infected bone marrow haematopoietic cells

Liu

Swaminathan

Yan

et al. 2019

Journal of General Virology

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CD34+ myeloid lineage progenitor cells are an important reservoir of latent human cytomegalovirus (HCMV), and differentiation to macrophages or dendritic cells (DCs) is known to cause reactivation of latent virus. Due to its species-specificity, murine models have been used to study mouse CMV (MCMV) latency and reactivation in vivo. While previous studies have shown that MCMV genomic DNA can be detected in the bone marrow (BM) of latently infected mice, the identity of these cells has not been defined. Therefore, we sought to identify and enrich for cellular sites of MCMV latency in the BM haematopoietic system, and to explore the potential for establishing an in vitro model for reactivation of latent MCMV. We studied the kinetics and cellular characteristics of acute infection and establishment of latency in the BM of mice. We found that while MCMV can infect a broad range of haematopoietic BM cells (BMCs), latent virus is only detectable in haematopoietic stem cells (HSCs), myeloid progenitor cells, monocytes and DC-enriched cell subsets. Using three separate approaches, MCMV reactivation was detected in association with differentiation into DC-enriched BMCs cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) followed by lipopolysaccharide (LPS) treatment. In summary, we have defined the kinetics and cellular profile of MCMV infection followed by the natural establishment of latency in vivo in the mouse BM haematopoietic system, including the haematopoietic phenotypes of cells that are permissive to acute infection, establish and harbour detectable latent virus, and can be stimulated to reactivate following DC enrichment and differentiation, followed by treatment with LPS.

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“…Amplification conditions were as follows: 95°C × 10 minutes, followed by 50 cycles of 95°C × 15 seconds, 62°C × 15 seconds, and 72°C × 60 seconds. The PCR assay used in this study can routinely detect 1 to 5 MCMV genome‐equivalents per reaction …”

Section: Methodsmentioning

confidence: 99%

“…The PCR assay used in this study can routinely detect 1 to 5 MCMV genome-equivalents per reaction. 29…”

Section: Pcr Amplification Of Tt-mcmv Dnamentioning

confidence: 99%

Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products

et al. 2014

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Transfusion‐transmitted cytomegalovirus (CMV) infections in a murine model: characterization of CMV‐infected donor mice

Cited by 9 publications

References 39 publications

Cytomegalovirus Hijacks CX3CR1hi Patrolling Monocytes as Immune-Privileged Vehicles for Dissemination in Mice

Cytomegalovirus Hijacks CX3CR1hi Patrolling Monocytes as Immune-Privileged Vehicles for Dissemination in Mice

A novel murine model of differentiation-mediated cytomegalovirus reactivation from latently infected bone marrow haematopoietic cells

Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products

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