scholarly journals Immunophenotyping and transcriptional profiling of human plasmablasts in dengue.

2021 ◽  
Author(s):  
Charu Aggarwal ◽  
Keshav Saini ◽  
Elluri Seetharami Reddy ◽  
Mohit Singla ◽  
Kaustuv Nayak ◽  
...  

Plasmablasts represent a specialized class of antibody secreting effector B cell population that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections leading to viral hemorrhagic fevers such as dengue or ebola. To gain a detailed understanding of the human plasmablast responses beyond antibody expression, here we performed immunophenotyping and RNA seq analysis of the plasmablasts from dengue febrile children in India. We found that the plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues including skin, mucosa, and intestine; and upregulated expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated expression of receptors for several B cell pro-survival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock compared to patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. Importance Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.

Author(s):  
Toshiaki Iba ◽  
JH Levy ◽  
Marcel Levi

A number of viral infectious diseases have emerged or reemerged from wildlife vectors that have generated serious threats to global health. Increased international traveling and commerce increase the risk of transmission of viral or other infectious diseases. In addition, recent climate changes accelerate the potential spread of domestic disease. The Coronavirus disease 2019 (COVID-19) pandemic is an important example of the worldwide spread, and the current epidemic will unlikely be the last. Viral hemorrhagic fevers, such as Dengue and Lassa fevers, may also have the potential to spread worldwide with a significant impact on public health with unpredictable timing. Based on the important lessons learned from COVID-19, it would be prudent to prepare for future pandemics of life-threatening viral diseases. Among the various threats, this review focuses on the coagulopathy of acute viral infections since hypercoagulability has been a major challenge in COVID-19, but represents a different presentation compared to viral hemorrhagic fever. However, both thrombosis and hemorrhage are understood as the result of thromboinflammation due to viral infections, and the role of anticoagulation is important to consider.


Author(s):  
Галина Компанец ◽  
Galina Kompanets

This paper includes review of innovative methods of monitoring of activity of natural foci of epidemically important for Russian Federation such viral infections as hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF), and the analysis of probability to control such «exotic» infections, as Denge fever and severe fever with thrombocytopenia syndrome (SFTS).


QRB Discovery ◽  
2020 ◽  
Vol 1 ◽  
Author(s):  
Shilei Hao ◽  
David Jin ◽  
Shuguang Zhang ◽  
Rui Qing

AbstractCytokine release syndrome (CRS), or ‘cytokine storm’, is the leading side effect during chimeric antigen receptor (CAR)-T therapy that is potentially life-threatening. It also plays a critical role in viral infections such as Coronavirus Disease 2019 (COVID-19). Therefore, efficient removal of excessive cytokines is essential for treatment. We previously reported a novel protein modification tool called the QTY code, through which hydrophobic amino acids Leu, Ile, Val and Phe are replaced by Gln (Q), Thr (T) and Tyr (Y). Thus, the functional detergent-free equivalents of membrane proteins can be designed. Here, we report the application of the QTY code on six variants of cytokine receptors, including interleukin receptors IL4Rα and IL10Rα, chemokine receptors CCR9 and CXCR2, as well as interferon receptors IFNγR1 and IFNλR1. QTY-variant cytokine receptors exhibit physiological properties similar to those of native receptors without the presence of hydrophobic segments. The receptors were fused to the Fc region of immunoglobulin G (IgG) protein to form an antibody-like structure. These QTY code-designed Fc-fusion receptors were expressed in Escherichia coli and purified. The resulting water-soluble fusion receptors bind to their respective ligands with Kd values affinity similar to isolated native receptors. Our cytokine receptor–Fc-fusion proteins potentially serve as an antibody-like decoy to dampen the excessive cytokine levels associated with CRS and COVID-19 infection.


2021 ◽  
Vol 3 (2) ◽  
pp. 01-15
Author(s):  
Makarius Tel Aviv C. Dela Cru ◽  
Benie T. Constantino IH

Dengue virus is the most common mosquito borne viral disease in humans, and poses a major challenge to global public health services. Infection can be caused by any of the 4 DENV serotypes, transmitted by female Aedes aegypti mosquitoes. Presenting features may vary from a mild self-limiting febrile illness to life-threatening symptoms of bleeding, organ impairment, and plasma leakage leading to shock. Early diagnosis and monitoring are critical to reduce mortality, especially in the context of the COVID-19 pandemic. Laboratory tests, such as the serological detection of either antigen or antibodies are useful in the diagnosis. Currently, although a vaccine for DENV is available, it remains a challenge to develop an effective vaccine against 4 discrete serotypes and antiviral drugs effective in reducing morbidity or improving disease outcome.


2021 ◽  
Author(s):  
Charu Aggarwal ◽  
Keshav Saini ◽  
Elluri Seetharami Reddy ◽  
Mohit Singla ◽  
Kaustuv Nayak ◽  
...  

Previous studies have shown that plasmablasts expand massively in dengue patients as compared to many other situations such as influenza infection or vaccination. However, a detailed understanding of the phenotypes and transcriptional features of these cells is lacking. Moreover, despite India having nearly a third of global dengue disease burden, there is virtually no information on plasmablasts responses in dengue patients from India. Here, we provide a detailed characterization of plasmablast responses from dengue confirmed febrile children in India. Immunophenotyping and RNA seq analysis showed that in addition to secreting dengue specific antibodies, these massively expanding cells expressed several adhesion molecules, chemokines and chemokine receptors that are involved in endothelial interactions, homing to skin or mucosal tissues including intestine. Surprisingly, we found that these cells also upregulated expression of several cytokine genes that are involved in angiogenesis, leukocyte extravasation and vascular permeability. These transcriptional features were qualitatively similar to plasmablasts from influenza vaccinees. Interestingly, the expansion of the plasmablasts in dengue patients was significantly lower in patients with primary dengue infection compared to those with secondary dengue. Moreover, within the primary dengue patients, their expansion was significantly lower in patients with mild dengue infection (DI) compared to patients with dengue with warning signs (DW) or severe dengue (SD). These results significantly improve our understanding of human plasmablast responses in dengue.


2017 ◽  
Vol 24 (08) ◽  
pp. 1216-1223
Author(s):  
Aneela Altaf Kidwai ◽  
Jamal Ara ◽  
Samina Ghaznawi ◽  
Shumaila Abdul Rasheed ◽  
Saleemullah Paracha ◽  
...  

Objectives: To determine the point of care role of dengue IgA and Dengue IgM/ IgG rapid diagnostic tests (RDTs) in a tertiary care setting in terms of day of onset of illness atpresentation and frequency of positive RDTs in dengue hemorrhagic fever (DHF) and dengueshock syndrome (DSS). Study Design: Cross-sectional study. Setting: Abbasi ShaheedHospital, Karachi. Period: August-2014 to January-2016. Method: Patients aged 13years andabove with acute febrile illness, fulfilling the WHO case definition criteria of probable DF andDHF were included. Two immunochromatograpic (ICT) based RDTs, Assure dengue IgA andPanbio Dengue Duo Cassette (IgM / IgG) were used. Dengue IgA was employed in all patientsfrom day 2 of illness whereas IgM / IgG was employed after day 4 of onset of fever. Result:Among 174 probable cases, 108 (62%) presented between 2 – 5 days of onset of fever, amongwhom 87 (80.5%) were found to be dengue IgA positive. Sixty-nine (39.65%) patients had DHF,among whom 97.1% were seropositive for IgA. Of 118 patients presented after 4 days of onsetof illness, 59.3% were positive by IgM / IgG rapid assay. Conclusion: Considering the higherfrequency of secondary dengue and DHF in dengue endemic-hyperendemic regions, IgAbased ICT might be a helpful diagnostic assay for early diagnosis of dengue infection.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Berta Nelly Restrepo ◽  
Mark E. Beatty ◽  
Yenny Goez ◽  
Ruth E. Ramirez ◽  
G. William Letson ◽  
...  

A dengue fever surveillance study was conducted at three medical facilities located in the low-income district of San Javier in Medellin, Colombia. During March 2008 to 2009, 781 patients with fever regardless of chief complaint were recruited for acute dengue virus infection testing. Of the 781 tested, 73 (9.3%) were positive for dengue infection. Serotypes DENV-2 (77%) and -3 (23%) were detected by PCR. One patient met the diagnostic criteria for dengue hemorrhagic fever. Only 3 out of 73 (4.1%) febrile subjects testing positive for dengue infection were diagnosed with dengue fever by the treating physician. This study confirms dengue virus as an important cause of acute febrile illness in Medellin, Colombia, but it is difficult to diagnose without dengue diagnostic testing.


2009 ◽  
Vol 4 (5) ◽  
pp. 315-321
Author(s):  
Masayuki Saijo ◽  
◽  
Shigeru Morikawa ◽  
Ichiro Kurane

Given the real possibility of hemorrhagic fever viruses such as ebola (EBOV), Marburg (MARV), Crimean-Congo hemorrhagic fever (CCHFV), and Lassa (LASV) viruses being introduced into virus-free nations such as Japan, the need arises for concomitant diagnostics even where such diseases are not endemic. Hemorrhagic fever viruses classified as biosafety level-4 (BSL-4) pathogens can only be manipulated in BSL-4 laboratories, making it difficult for nations such as Japan, having no BSL-4 laboratories, to develop required diagnostic assays. To circumvent this problem, diagnostic assays with recombinant viral antigens have been developed at the National Institute of Infectious Diseases, Tokyo, Japan (NIID). Diagnostics such as enzyme immunoassays for detecting viral hemorrhagic antibodies and antigens were developed using recombinant nucleoproteins (rNPs) of EBOV, MARV, CCHFV, and LASV for use as antigens. Immunoglobulin-G (IgG)-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay using rNPs were confirmed to be highly sensitive and specific in detecting these antibodies. Sandwich antigen (Ag) capture ELISA was also developed for detecting these antigens. The sections that follow detail diagnostics developed at the NIID.


CJEM ◽  
1999 ◽  
Vol 1 (02) ◽  
pp. 130-131
Author(s):  
Garth Dickinson

African hemorrhagic fevers are lethal, incurable viral infections with a notorious propensity to afflict health care workers. Lassa and Ebola are the best-known culprits, and these killers spread fear well beyond their geographic range. Chances are your hospital has a plan to deal with febrile travellers returning from endemic regions of Africa. Such plans involve isolation, space suit technology and desperate calls to public health and tropical disease experts.


2001 ◽  
Vol 7 (S2) ◽  
pp. 166-167
Author(s):  
Sherif R. Zaki ◽  
Cynthia S. Goldsmith

Clinically, the combination of fever and hemorrhage can be caused by many pathogens, including viruses, rickettsiae, bacteria, protozoans, and fungi. However, the term viral hemorrhagic fever (VHF) is usually reserved for systemic infections characterized by fever and hemorrhage caused by a special group of viruses that belong to four different families: Filoviridae, Arenaviridae, Bunyaviridae, and Flaviviridae. All members are lipid-enveloped RNA viruses; except for filoviruses, where the resorvoir remains unknown, these viruses are transmitted to humans by arthropods and rodents. The VHFs are characterized by abnormal vascular regulation and damage. The VHFs all have similar clinical pictures with mortality rates of 15-30% or in the case of Ebola virus, up to 80%. Between 1993 and 2001, more different VHFs and related diseases were reported than during any comparable period over the past several decades. These diseases include Ebola VHF in Uganda in 2000, in Zaire in 1995 and in Gabon between 1994 and 1996; ongoing cases of Marburg hemorrhagic fever in the Democratic Republic of Congo beginning in 1998; Rift Valley fever in Saudi Arabia and Yemen in 2000 and in Kenya in 1997; Lassa fever in Sierra Leone in 1997; hantavirus pulmonary syndrome in the Americas since 1993; and imported cases of dengue hemorrhagic fever from Central and South America, and yellow fever from Africa during the 1990s.


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