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Article ; Online: Susceptibility and cytokine responses of human neuronal cells to multiple circulating EV-A71 genotypes in India.

Mohanty, Madhu Chhanda / Varose, Swapnil Yashavant / Saxena, Vinay Kumar

2021 Volume 11, Issue 1, Page(s) 17751

Abstract: Enterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia-Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and G) were ... ...

Abstract	Enterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia-Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and G) were isolated in India in recent years, no recognizable outbreak of EV-A71 caused HFMD, Acute Flaccid paralysis (AFP) or encephalitis have been reported so far. It is essential to study the pathogenicity or cell tropism of these Indian isolates in order to understand their tendency to cause disease. We investigated the susceptibility and cytokine responses of indigenous EV-A71 genotypes (D and G) isolated from cases of AFP and genotype C viruses isolated from cases of HFMD and encephalitis, in human cells in-vitro. Although all three EV-A71 genotypes could infect and replicate in human muscle and neuronal cells, the genotype D virus showed a delayed response in human neuronal cells. Quantification of cytokine secretion in response to these isolates followed by confirmation with gene expression assays in human neuronal cells revealed significantly higher secretion of pro-inflammatory cytokines TNF-α IL-8, IL-6, IP-10 (p < 0.001) in G genotype infected cells as compared to pathogenic C genotypes whereas the genotype D virus could not induce any of the inflammatory cytokines. These findings will help to better understand the host response to indigenous EV-A71 genotypes for management of future EV-A71 outbreaks in India, if any.
MeSH term(s)	Acute Disease ; Adult ; Cell Line, Tumor ; Child ; Cytokines/biosynthesis ; Cytokines/genetics ; Cytopathogenic Effect, Viral ; Disease Outbreaks ; Disease Susceptibility ; Encephalitis, Viral/epidemiology ; Encephalitis, Viral/virology ; Enterovirus A, Human/classification ; Enterovirus A, Human/genetics ; Enterovirus A, Human/isolation & purification ; Enterovirus A, Human/pathogenicity ; Female ; Gene Expression Regulation, Viral ; Genotype ; Hand, Foot and Mouth Disease/epidemiology ; Hand, Foot and Mouth Disease/virology ; Humans ; India/epidemiology ; Male ; Middle Aged ; Neurons/metabolism ; Neurons/virology ; Paraplegia/epidemiology ; Paraplegia/virology ; Viral Tropism
Chemical Substances	Cytokines
Language	English
Publishing date	2021-09-07
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-97166-x
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Article ; Online: Susceptibility and cytokine responses of human neuronal cells to multiple circulating EV-A71 genotypes in India

Madhu Chhanda Mohanty / Swapnil Yashavant Varose / Vinay Kumar Saxena

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract Enterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia–Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and ...

Abstract	Abstract Enterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia–Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and G) were isolated in India in recent years, no recognizable outbreak of EV-A71 caused HFMD, Acute Flaccid paralysis (AFP) or encephalitis have been reported so far. It is essential to study the pathogenicity or cell tropism of these Indian isolates in order to understand their tendency to cause disease. We investigated the susceptibility and cytokine responses of indigenous EV-A71 genotypes (D and G) isolated from cases of AFP and genotype C viruses isolated from cases of HFMD and encephalitis, in human cells in-vitro. Although all three EV-A71 genotypes could infect and replicate in human muscle and neuronal cells, the genotype D virus showed a delayed response in human neuronal cells. Quantification of cytokine secretion in response to these isolates followed by confirmation with gene expression assays in human neuronal cells revealed significantly higher secretion of pro-inflammatory cytokines TNF-α IL-8, IL-6, IP-10 (p < 0.001) in G genotype infected cells as compared to pathogenic C genotypes whereas the genotype D virus could not induce any of the inflammatory cytokines. These findings will help to better understand the host response to indigenous EV-A71 genotypes for management of future EV-A71 outbreaks in India, if any.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Prolonged Fecal Shedding of SARS-CoV-2 in Asymptomatic Children with Inborn Errors of Immunity.

Mohanty, Madhu Chhanda / Taur, Prasad D / Sawant, Unnati Prashant / Yadav, Reetika Malik / Potdar, Varsha

Journal of clinical immunology

2021 Volume 41, Issue 8, Page(s) 1748–1753

MeSH term(s)	Asymptomatic Infections ; COVID-19/virology ; Child ; Child, Preschool ; Feces/virology ; Female ; Genetic Diseases, Inborn/immunology ; Genetic Diseases, Inborn/virology ; Humans ; Immunologic Deficiency Syndromes/immunology ; Immunologic Deficiency Syndromes/virology ; Infant ; Male ; SARS-CoV-2/isolation & purification ; Virus Shedding
Language	English
Publishing date	2021-09-16
Publishing country	Netherlands
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-021-01132-1
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Article: Expression of innate immune response genes in upper airway samples of SARS-CoV-2 infected patients: A preliminary study.

Mohanty, Madhu Chhanda / Varose, Swapnil Yashwant / Sawant, Unnati Prashant / Fernandes, Mevis Minin

The Indian journal of medical research

2021 Volume 153, Issue 5&6, Page(s) 677–683

Abstract: Background & objectives: Upper respiratory mucosa is the entryway for SARS-CoV-2, and cells at this site form the first line of resistance against the pathogens. Innate immune response at this point is crucial for managing the replication and early ... ...

Abstract	Background & objectives: Upper respiratory mucosa is the entryway for SARS-CoV-2, and cells at this site form the first line of resistance against the pathogens. Innate immune response at this point is crucial for managing the replication and early stage symptoms of virus infection. This study was aimed to evaluate the expression of pattern recognition receptors and cytokines in upper airway cells of SARS-CoV-2 infected patients. Methods: Forty seven nasopharyngeal swab (NPS) specimens from 25 SARS-CoV-2 infected patients and 22 SARS-CoV-2 negative individuals were investigated for expression of toll-like receptors (TLRs), melanoma differentiation-associated protein 5 (MDA5), NOD-like receptors family pyrin domain containing 3 (NLRP3), angiotensin-converting enzyme 2 (ACE2), interleukin (IL) - 6, tumour necrosis factor alpha (TNFα) and type-1 interferons (IFNs) by real time reverse transcription polymerase chain reaction. Results: Increased expression of TLR2, MDA5 and ACE2 was detected in SARS-CoV-2 infected patients in comparison with controls. MDA5 expression was significantly higher in asymptomatic and mildly symptomatic SARS-CoV-2 positive patients than the patients with severe symptoms. The asymptomatic group showed significant induction of type 1 IFNs than the symptomatic group. Non-specific induction of TLR7 could be observed in nasopharyngeal (NP) cells irrespective of symptoms and SARS-CoV-2 positivity. Interpretation & conclusions: The findings suggest that increased MDA5 in NP cells of asymptomatic SARS-CoV-2 positive patients may subsequently induce type 1 IFNs to protect the individuals from further clinical severity of SARS-CoV-2 infection. A future prospective study in NPS of larger cohort needs to be performed to confirm our findings.
MeSH term(s)	COVID-19 ; Cytokines/genetics ; Humans ; Immunity, Innate/genetics ; Interferon-Induced Helicase, IFIH1/genetics ; SARS-CoV-2
Chemical Substances	Cytokines ; IFIH1 protein, human (EC 3.6.1.-) ; Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13)
Language	English
Publishing date	2021-09-10
Publishing country	India
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390883-5
ISSN	0971-5916 ; 0019-5340
ISSN	0971-5916 ; 0019-5340
DOI	10.4103/ijmr.IJMR_131_21
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Article ; Online: Expression of innate immune response genes in upper airway samples of SARS-CoV-2 infected patients

Madhu Chhanda Mohanty / Swapnil Yashwant Varose / Unnati Prashant Sawant / Mevis Minin Fernandes

Indian Journal of Medical Research, Vol 153, Iss 5, Pp 677-

A preliminary study

2021 Volume 683

Abstract	Background & objectives: Upper respiratory mucosa is the entryway for SARS-CoV-2, and cells at this site form the first line of resistance against the pathogens. Innate immune response at this point is crucial for managing the replication and early stage symptoms of virus infection. This study was aimed to evaluate the expression of pattern recognition receptors and cytokines in upper airway cells of SARS-CoV-2 infected patients. Methods: Forty seven nasopharyngeal swab (NPS) specimens from 25 SARS-CoV-2 infected patients and 22 SARS-CoV-2 negative individuals were investigated for expression of toll-like receptors (TLRs), melanoma differentiation-associated protein 5 (MDA5), NOD-like receptors family pyrin domain containing 3 (NLRP3), angiotensin-converting enzyme 2 (ACE2), interleukin (IL) - 6, tumour necrosis factor alpha (TNFα) and type-1 interferons (IFNs) by real time reverse transcription polymerase chain reaction. Results: Increased expression of TLR2, MDA5 and ACE2 was detected in SARS-CoV-2 infected patients in comparison with controls. MDA5 expression was significantly higher in asymptomatic and mildly symptomatic SARS-CoV-2 positive patients than the patients with severe symptoms. The asymptomatic group showed significant induction of type 1 IFNs than the symptomatic group. Non-specific induction of TLR7 could be observed in nasopharyngeal (NP) cells irrespective of symptoms and SARS-CoV-2 positivity. Interpretation & conclusions: The findings suggest that increased MDA5 in NP cells of asymptomatic SARS-CoV-2 positive patients may subsequently induce type 1 IFNs to protect the individuals from further clinical severity of SARS-CoV-2 infection. A future prospective study in NPS of larger cohort needs to be performed to confirm our findings.
Keywords	innate immunity - mda-5 - nasopharyngeal swab - sars-cov-2 - toll-like receptors ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Poliovirus surveillance in patients with primary immunodeficiencies, India.

Mohanty, Madhu Chhanda / Mohammad, Ahmad / Verma, Harish / Kumar, Arun / Madkaikar, Manisha Ranjan / Desai, Mukesh / Varose, Swapnil Yashwant / Sawant, Unnati / Yadav, Reetika Malik / Taur, Prasad / Kathuria, Rachana / Tatkare, Manogat / Murhekar, Megh / Haldar, Pradeep / Abraham, Priya

Bulletin of the World Health Organization

2023 Volume 101, Issue 5, Page(s) 346–354

Abstract: Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of ... ...

Abstract	Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future.
MeSH term(s)	Humans ; Poliovirus ; Poliomyelitis/epidemiology ; Poliomyelitis/prevention & control ; India/epidemiology ; Immunologic Deficiency Syndromes/complications ; Immunologic Deficiency Syndromes/epidemiology ; Primary Immunodeficiency Diseases ; Population Surveillance/methods
Language	English
Publishing date	2023-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	80213-x
ISSN	1564-0604 ; 0042-9686 ; 0366-4996 ; 0510-8659
ISSN (online)	1564-0604
ISSN	0042-9686 ; 0366-4996 ; 0510-8659
DOI	10.2471/BLT.22.289066
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Journal ; Article ; Online: Poliovirus surveillance in patients with primary immunodeficiencies, India

2023

Abstract: ... 346 ... ...

Abstract	346 354
Keywords	Policy & Practice
Publisher	World Health Organization
Document type	Journal ; Article ; Online
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Article: Assessment of Enterovirus Excretion and Identification of VDPVs in Patients with Primary Immunodeficiency in India: Outcome of ICMR-WHO Collaborative Study Phase-I.

Vaccines

2023 Volume 11, Issue 7

Abstract: The emergence of vaccine-derived polioviruses (VDPVs) in patients with Primary Immunodeficiency (PID) is a threat to the polio-eradication program. In a first of its kind pilot study for successful screening and identification of VDPV excretion among ... ...

Abstract	The emergence of vaccine-derived polioviruses (VDPVs) in patients with Primary Immunodeficiency (PID) is a threat to the polio-eradication program. In a first of its kind pilot study for successful screening and identification of VDPV excretion among patients with PID in India, enteroviruses were assessed in stool specimens of 154 PID patients across India in a period of two years. A total of 21.42% of patients were tested positive for enteroviruses, 2.59% tested positive for polioviruses (PV), whereas 18.83% of patients were positive for non-polio enteroviruses (NPEV). A male child of 3 years and 6 months of age diagnosed with Hyper IgM syndrome was detected positive for type1 VDPV (iVDPV1) with 1.6% nucleotide divergence from the parent Sabin strain. E21 (19.4%), E14 (9%), E11 (9%), E16 (7.5%), and CVA2 (7.5%) were the five most frequently observed NPEV types in PID patients. Patients with combined immunodeficiency were at a higher risk for enterovirus infection as compared to antibody deficiency. The high susceptibility of PID patients to enterovirus infection emphasizes the need for enhanced surveillance of these patients until the use of OPV is stopped. The expansion of PID surveillance and integration with a national program will facilitate early detection and follow-up of iVDPV excretion to mitigate the risk for iVDPV spread.
Language	English
Publishing date	2023-07-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11071211
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Article ; Online: Natural Clearance of Prolonged VDPV Infection in a Child With Primary Immunodeficiency Disorder.

Mohanty, Madhu Chhanda / Madkaikar, Manisha Ranjan / Desai, Mukesh / Aluri, Jahnavi / Varose, Swapnil Yashwant / Taur, Prasad / Sharma, Deepa Kailash / Nalavade, Uma Prajwal / Rane, Sneha Vijay / Gupta, Maya / Shabarish, Snehal / Dalvi, Aparna / Deshpande, Jagadish Mohanrao

Frontiers in immunology

2019 Volume 10, Page(s) 1567

Abstract: The emergence of immunodeficiency-associated vaccine-derived polioviruses (iVDPV) from children with primary immunodeficiency disorders poses a threat to the eradication program. Herein, we report a patient with severe combined immunodeficiency (SCID), ... ...

Abstract	The emergence of immunodeficiency-associated vaccine-derived polioviruses (iVDPV) from children with primary immunodeficiency disorders poses a threat to the eradication program. Herein, we report a patient with severe combined immunodeficiency (SCID), identified as a prolonged serotype 3 iVDPV (iVDPV3) excreter with 13 VDPV3 isolates and a maximum of 10.33% nucleotide divergence, who abruptly cleared infection after a period of 2 years. Occurrence of an episode of norovirus diarrhea associated with increased activated oligoclonal cytotoxic T cells, inverse CD4:CD8 ratio, significantly elevated pro-inflammatory cytokines, and subsequent clearance of the poliovirus suggests a possible link between inflammatory diarrheal illness and clearance of iVDPV. Our findings suggest that in the absence of B cells and sufficiently activated T/NK cells, macrophages and other T cells may produce auto-inflammatory conditions by TLR/RLR ligands expressed by previous/ongoing bacterial or viral infections to clear VDPV infection. The study highlights the need to screen all the patients with combined immunodeficiency for poliovirus excretion and intermittent follow-up of their immune parameters if found positive, in order to manage the risk of iVDPV excretion in the polio eradication endgame strategy.
MeSH term(s)	Age Factors ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Child, Preschool ; Cytokines/blood ; Humans ; Immunoglobulins/blood ; Male ; Poliovirus/genetics ; Poliovirus/immunology ; Poliovirus Vaccine, Oral/adverse effects ; Poliovirus Vaccine, Oral/immunology ; Primary Immunodeficiency Diseases/blood ; Primary Immunodeficiency Diseases/diagnosis ; Primary Immunodeficiency Diseases/etiology ; Primary Immunodeficiency Diseases/therapy ; Serologic Tests ; Symptom Assessment ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Vaccination/adverse effects
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Cytokines ; Immunoglobulins ; Poliovirus Vaccine, Oral
Language	English
Publishing date	2019-07-23
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.01567
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Article ; Online: Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.

Mohanty, Madhu Chhanda / Madkaikar, Manisha Rajan / Desai, Mukesh / Taur, Prasad / Nalavade, Uma Prajwal / Sharma, Deepa Kailash / Gupta, Maya / Dalvi, Aparna / Shabrish, Snehal / Kulkarni, Manasi / Aluri, Jahnavi / Deshpande, Jagadish Mohanrao

Emerging infectious diseases

2017 Volume 23, Issue 10, Page(s) 1664–1670

Abstract: Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study ... ...

Abstract	Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2310.170724
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