Neuroinvasion of influenza A/H3N2: a fatal case in an immunocompetent adult

Fernández-Blázquez, Ana; Castañón-Apilánez, Maria; Álvarez-Argüelles, Marta Elena; Sabater-Cabrera, Christian; Rojo‐Alba, Susana; Boga, José Antonio; Tassa, Germán Morís de la; Fernández, B.; Melón, Santiago

doi:10.1007/s13365-018-0690-9

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…Pandemic H1N1 and seasonal H3N2 viruses are occasionally detected in the CNS or CSF in humans and from experimentally inoculated ferrets and mice, even though pH1N1 and H3N2 viruses only replicated in SK-N-SH cells in the presence of trypsin (11–15, 67–70). However, these viruses are rarely isolated in high titers or detected by immunohistochemistry in the CNS of humans or experimentally inoculated ferrets and mice, indicating that these viruses might be able to enter the CNS but that replication is inefficient.…”

Section: Discussionmentioning

confidence: 99%

“…This is, however, less frequently observed (2, 4). Influenza A viruses, hereinafter referred to as influenza virus, have been linked to CNS disease since the 1918 H1N1 pandemic (5, 6), and CNS disease has been observed during all subsequent pandemics (7–12) as well as during seasonal epidemics, with sporadic detection of influenza virus in the CNS or cerebral spinal fluid (CSF) of humans (13–15). Zoonotic influenza viruses only occasionally infect humans, but when they do, they are frequently associated with severe and systemic disease (1).…”

Section: Introductionmentioning

confidence: 99%

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Viral Factors Important for Efficient Replication of Influenza A Viruses in Cells of the Central Nervous System

Siegers

Bildt

Zhu

et al. 2019

J Virol

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Central nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections. Remarkably, zoonotic H5N1 virus infections are more frequently associated with CNS disease than seasonal or pandemic influenza viruses. Little is known about the interaction between influenza A viruses and cells of the CNS; therefore, it is currently unknown which viral factors are important for efficient replication. Here, we determined the replication kinetics of a seasonal, pandemic, zoonotic, and lab-adapted influenza A virus in human neuron-like (SK-N-SH) and astrocyte-like (U87-MG) cells and primary mouse cortex neurons. In general, highly pathogenic avian influenza (HPAI) H5N1 virus replicated most efficiently in all cells, which was associated with efficient attachment and infection. Seasonal H3N2 and to a lesser extent pandemic H1N1 virus replicated in a trypsin-dependent manner in SK-N-SH but not in U87-MG cells. In the absence of trypsin, only HPAI H5N1 and WSN viruses replicated. Removal of the multibasic cleavage site (MBCS) from HPAI H5N1 virus attenuated, but did not abrogate, replication. Taken together, our results showed that the MBCS and, to a lesser extent, the ability to attach are important determinants for efficient replication of HPAI H5N1 virus in cells of the CNS. This suggests that both an alternative hemagglutinin (HA) cleavage mechanism and preference for α-2,3-linked sialic acids allowing efficient attachment contribute to the ability of influenza A viruses to replicate efficiently in cells of the CNS. This study further improves our knowledge on potential viral factors important for the neurotropic potential of influenza A viruses. IMPORTANCE Central nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections, and the frequency and severity differ between seasonal, pandemic, and zoonotic influenza viruses. However, little is known about the interaction of these viruses with cells of the CNS. Differences among seasonal, pandemic, and zoonotic influenza viruses in replication efficacy in CNS cells, in vitro, suggest that the presence of an alternative HA cleavage mechanism and ability to attach are important viral factors. Identifying these viral factors and detailed knowledge of the interaction between influenza virus and CNS cells are important to prevent and treat this potentially lethal CNS disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viral Factors Important for Efficient Replication of Influenza A Viruses in Cells of the Central Nervous System

Siegers

Bildt

Zhu

et al. 2019

J Virol

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“…Influenza A H3N2 was later detected in a nasopharyngeal swab, and the patient underwent emergency decompressive craniectomy. The patient had a poor clinical evolution and died 72 hours after ICU admission [ 29 ].…”

Section: Reviewmentioning

confidence: 99%

Exploring the Correlation Between Influenza A Virus (H3N2) Infections and Neurological Manifestations: A Scoping Review

Reddy¹,

CA²,

Kandi³

et al. 2023

Cureus

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Influenza A virus (IAV), particularly the H3N2 variant, is known to cause respiratory manifestations, but it can also lead to neurological complications ranging from mild symptoms like headache and dizziness to severe conditions such as encephalitis and acute necrotizing encephalopathy (ANE). In this article, the correlation between the H3N2 variant of the IAV and neurological manifestations is discussed. Additionally, prompt recognition and treatment of influenza-associated neurological manifestations are highlighted to prevent infection-related long-term complications. This review briefly discusses various neurological complications linked to IAV infections, such as encephalitis, febrile convulsions, and acute disseminated encephalomyelitis, and the potential mechanisms involved in the development of neurological complications.

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Fatal case of simply influenza A (H3N2)-associated encephalitis in immunocompetent patient

Martínez‐Dubarbie

Ortega-Valín

Gonzalez-Quintanilla

et al. 2021

Clinical Neurology and Neurosurgery

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Neuroinvasion of influenza A/H3N2: a fatal case in an immunocompetent adult

Cited by 8 publications

References 17 publications

Viral Factors Important for Efficient Replication of Influenza A Viruses in Cells of the Central Nervous System

Viral Factors Important for Efficient Replication of Influenza A Viruses in Cells of the Central Nervous System

Exploring the Correlation Between Influenza A Virus (H3N2) Infections and Neurological Manifestations: A Scoping Review

Fatal case of simply influenza A (H3N2)-associated encephalitis in immunocompetent patient

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