Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar

Aye, Khin Saw; Charngkaew, Komgrid; Win, Ne; Wai, Kyaw Zin; Moe, Kyaw Kyaw; Punyadee, Nuntaya; Thiemmeca, Somchai; Suttitheptumrong, Aroonroong; Sukpanichnant, Sanya; Malasit, Prida; Halstead, Scott B.

doi:10.1016/j.humpath.2014.01.022

Cited by 151 publications

(159 citation statements)

References 22 publications

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“…These MPs harbored viral E and NS1 on their surfaces. Electron microscopy techniques, including negative staining and immunogold labeling, revealed greater detail about the MPs generated from hepatocytes (one of the major target cells for DENV replication in vivo [43]), which were morphologically distinct from the virions produced in the same culture system. Nevertheless, the molecular mechanism underlying MP generation after DENV infection is still unknown, that is, whether it is directly linked to the process of cells undergoing apoptosis or it is a consequence of cell activation in response to viral infection leading to increased intracellular calcium, which in turn causes membrane vesiculation.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that the transport of ICs for clearance in the liver and spleen in dengue patients might be defective due to the pathology of those organs directly caused by DENV infection. Indeed, a recent pathology study at autopsy of tissues obtained from patients who have died from DHF/DSS, led by our group, has demonstrated that the liver and spleen are the two major organs found to be heavily infected (43). Alternatively, the amount and nature of ICs, including their size and whether they are soluble or cell associated, determine the magnitude and efficiency of complement fixation (70) and may also influence the degree of MP shedding from RBCs.…”

Section: Cd235mentioning

confidence: 99%

See 1 more Smart Citation

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Punyadee

Mairiang

Thiemmeca

et al. 2015

J Virol

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Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1-anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. IMPORTANCEDengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. E ach year, up to 390 million people are infected by dengue virus (DENV), the most significant mosquito-borne virus of the Flaviviridae family, posing serious socioeconomic and health burdens globally (1). Four serotypes of viruses (DENV serotype 1 [DENV-1], DENV-2, DENV-3, and DENV-4) are transmitted to humans by Aedes mosquitoes to establish both endemic and epidemic transmission cycles primarily in tropical and subtropical countries (1). Although the majority of DENV infections in humans are subclinical, a small fraction of infected individuals develops clinical symptoms ranging from a self-...

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Section: Discussionmentioning

confidence: 99%

Section: Cd235mentioning

confidence: 99%

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Punyadee

Mairiang

Thiemmeca

et al. 2015

J Virol

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“…DENV infects several organs in humans, altering host homeostasis and counteracting the host response (Aye et al, 2014;Pó voa et al, 2014). These events suggest complex interactions between host and virus where viral proteins play roles in several networks.…”

Section: Tap-tagged Dengue Virus and Host-virus Interactionsmentioning

confidence: 99%

Development of viable TAP-tagged dengue virus for investigation of host–virus interactions in viral replication

Poyomtip

Hodge

Matangkasombut

et al. 2016

Journal of General Virology

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Dengue virus (DENV) is a mosquito-borne flavivirus responsible for life-threatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The viral replication machinery containing the core non-structural protein 5 (NS5) is implicated in severe dengue symptoms but molecular details remain obscure. To date, studies seeking to catalogue and characterize interaction networks between viral NS5 and host proteins have been limited to the yeast twohybrid system, computational prediction and co-immunoprecipitation (IP) of ectopically expressed NS5. However, these traditional approaches do not reproduce a natural course of infection in which a number of DENV NS proteins colocalize and tightly associate during the replication process. Here, we demonstrate the development of a recombinant DENV that harbours a TAP tag in NS5 to study host-virus interactions in vivo. We show that our engineered DENV was infective in several human cell lines and that the tags were stable over multiple viral passages, suggesting negligible structural and functional disturbance of NS5. We further provide proof-of-concept for the use of rationally tagged virus by revealing a high confidence NS5 interaction network in human hepatic cells. Our analysis uncovered previously unrecognized hnRNP complexes and several low-abundance fatty acid metabolism genes, which have been implicated in the viral life cycle. This study sets a new standard for investigation of host-flavivirus interactions.

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“…There is limited information on DENV-infected human tissue biopsies, since postmortems are rarely conducted on mortality cases (9). Serum viral load (viremia), the current clinical diagnostic gold standard, does not always correlate with disease severity, nor does it robustly inform to anti-dengue therapy response under strict clinical trial conditions (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response

Chacko¹,

Watanabe

Herr³

et al. 2017

JCI Insight

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Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar

Cited by 151 publications

References 22 publications

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

Development of viable TAP-tagged dengue virus for investigation of host–virus interactions in viral replication

18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response

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