Lethal Avian Influenza A (H5N1) Virus Infects Pontomedullary Nuclei Containing Chemo‐sensitive Neurons to Induce Depressed Hypercapnic Ventilatory Response (dHCVR) in Mice

The highly pathogenic H5N1 (HK483) viral infection causes a depressed hypercapnic ventilatory response (dHCVR, 20%↓) at 2 days postinfection (dpi) and death at 7 dpi in mice, but the relevant mechanisms are not fully understood. Glomus cells in the carotid body and catecholaminergic neurons in locus coeruleus (LC), neurokinin 1 receptor (NK1R)-expressing neurons in the retrotrapezoid nucleus (RTN), and serotonergic neurons in the raphe are chemosensitive and responsible for HCVR. We asked whether the dHCVR became worse over the infection period with viral replication in these cells/neurons. Mice intranasally inoculated with saline or the HK483 virus were exposed to hypercapnia for 5 min at 0, 2, 4, or 6 dpi, followed by immunohistochemistry to determine the expression of nucleoprotein of H5N1 influenza A (NP) alone and coupled with 1) tyrosine hydroxylase (TH) in the carotid body and LC, 2) NK1R in the RTN, and 3) tryptophan hydroxylase (TPH) in the raphe. HK483 viral infection blunted HCVR by ∼20, 50, and 65% at 2, 4, and 6 dpi. The NP was observed in the pontomedullary respiratory-related nuclei (but not in the carotid body) at 4 and 6 dpi, especially in 20% of RTN NK1R, 35% of LC TH, and ∼10% raphe TPH neurons. The infection significantly reduced the local NK1R or TPH immunoreactivity and population of neurons expressing NK1R or TPH. We conclude that the HK483 virus infects the pontomedullary respiratory nuclei, particularly chemosensitive neurons in the RTN, LC, and raphe, contributing to the severe depression of HCVR and respiratory failure at 6 dpi.

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Laboratory investigation of the first suspected human cases of infection with avian influenza A(H5N1) virus in Bulgaria

Eurosurveillance ◽

10.2807/ese.13.30.18938-en ◽

2008 ◽

Vol 13 (30) ◽

Author(s):

T Hadzhiolova ◽

S Pavlova ◽

R Kotseva

Keyword(s):

Avian Influenza ◽

Influenza A ◽

H5n1 Virus ◽

Close Contact ◽

National Laboratory ◽

Respiratory Illness ◽

H1n1 Influenza ◽

Rt Pcr ◽

Public Attention ◽

H5n1 Influenza

Reports of human cases of infection with avian influenza A(H5N1) virus have received increased public attention because of the potential for the emergence of a pandemic strain. In the end of 2005 and the beginning of 2006, avian influenza A(H5N1) virus caused outbreaks among domestic poultry and was isolated from wild swans in many European countries, including Bulgaria. Between January and March 2006, samples were collected from 26 patients who had been in close contact with ill or dead birds and developed a subsequent respiratory illness. The testing took place at the National Laboratory of Influenza in Sofia. Specific ?(H5N1) assays were applied for screening (Sacace RT-PCR and real-time kit). Avian flu ?(H5N1) virus was not detected in any of the patients tested. In three patients, human subtype ?(H1N1) influenza virus, identifiable by RT-PCR was isolated and further characterized by hemagglutination inhibition test (HIT). The reliability of the molecular assays used in this investigation was demonstrated in an International Quality Control for Human and Avian ?(H5N1) Influenza performed later in 2006 by INSTAND (Society for Promotion of Quality Assurance in the Medical Laboratories), Germany.

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Avian Influenza A(H5N1) Virus Outbreak Investigation: Application of the FAO-OIE-WHO Four-way Linking Framework in Indonesia

Zoonoses and Public Health ◽

10.1111/zph.12158 ◽

2014 ◽

Vol 62 (5) ◽

pp. 381-387 ◽

Cited By ~ 9

Author(s):

V. Setiawaty ◽

N. L. P. I. Dharmayanti ◽

Misriyah ◽

H. A. Pawestri ◽

M. Azhar ◽

...

Keyword(s):

Avian Influenza ◽

Influenza A ◽

H5n1 Virus ◽

Outbreak Investigation

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Pathology of an outbreak of highly pathogenic avian influenza A(H5N1) virus of clade 2.3.2.1a in turkeys in Bangladesh

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638720965540 ◽

2020 ◽

Vol 33 (1) ◽

pp. 124-128

Author(s):

Tanjin T. Mumu ◽

Mohammed Nooruzzaman ◽

Azmary Hasnat ◽

Rokshana Parvin ◽

Emdadul H. Chowdhury ◽

...

Keyword(s):

Avian Influenza ◽

Influenza A ◽

H5n1 Virus ◽

Highly Pathogenic Avian Influenza ◽

Clinical Signs ◽

Bursa Of Fabricius ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza ◽

Brain Hemorrhages ◽

The Brain

A mixed-aged flock of 130 turkeys in Bangladesh reported the sudden death of 1 bird in September 2017. Highly pathogenic avian influenza A(H5N1) virus was detected in 3 turkeys, and phylogenetic analysis placed the viruses in the reassortant clade 2.3.2.1a. The birds had clinical signs of depression, diarrhea, weakness, closed eyes, and finally death. The mortality rate of the flock was 13% over the 6 d prior to the flock being euthanized. At autopsy, we observed congestion in lungs and brain, hemorrhages in the trachea, pancreas, breast muscle, coronary fat, intestine, bursa of Fabricius, and kidneys. Histopathology revealed hemorrhagic pneumonia, hemorrhages in the liver and kidneys, and hemorrhages and necrosis in the spleen and pancreas. Significant changes in the brain included gliosis, focal encephalomalacia and encephalitis, and neuronophagia.

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