scholarly journals Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets

2013 ◽  
Vol 87 (17) ◽  
pp. 9911-9922 ◽  
Author(s):  
H. Zaraket ◽  
O. A. Bridges ◽  
S. Duan ◽  
T. Baranovich ◽  
S.-W. Yoon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Upper Respiratory Tract ◽  
H5n1 Influenza Virus ◽  
Acid Stability ◽  
Virus Growth ◽  
H5n1 Influenza ◽  
Hemagglutinin Protein ◽  
Upper Respiratory

scholarly journals Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

2015 ◽  
Vol 90 (4) ◽  
pp. 1888-1897 ◽  
Author(s):  
Kathryn M. Edenborough ◽  
Suzanne Lowther ◽  
Karen Laurie ◽  
Manabu Yamada ◽  
Fenella Long ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Severe Disease ◽  
Upper Respiratory Tract ◽  
H5n1 Influenza Virus ◽  
Viral Spread ◽  
H5n1 Influenza ◽  
Upper Respiratory ◽  
The Brain

ABSTRACTAlthough avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease.IMPORTANCERisks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus could spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower after exposure to virus by this route than when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection, such as viremia, could help prioritize antiviral treatments for patients most at risk of succumbing to infection.

scholarly journals Identification of Influenza A Virus PB2 Residues Involved in Enhanced Polymerase Activity and Virus Growth in Mammalian Cells at Low Temperatures

2015 ◽  
Vol 89 (15) ◽  
pp. 8042-8049 ◽  
Author(s):  
Tsuyoshi Hayashi ◽  
Saintedym Wills ◽  
Kendra A. Bussey ◽  
Toru Takimoto
Keyword(s):  
Influenza Virus ◽  
Low Temperature ◽  
Respiratory Tract ◽  
Mammalian Cells ◽  
Influenza A ◽  
Polymerase Activity ◽  
Upper Respiratory Tract ◽  
Virus Growth ◽  
Avian Origin ◽  
Upper Respiratory

ABSTRACTMutations in the polymerase genes are known to play a major role in avian influenza virus adaptation to mammalian hosts. Despite having avian origin PA and PB2, the 2009 pandemic H1N1 virus (pH1N1) can replicate well in mammalian respiratory tracts, suggesting that these proteins have acquired mutations for efficient growth in humans. We have previously shown that PA from the pH1N1 virus A/California/04/09 (Cal) strongly enhances activity of an otherwise avian polymerase complex derived from A/chicken/Nanchang/3-120/01 (Nan) in mammalian cells. However, this enhancement was observed at 37°C but not at the lower temperature of 34°C. An additional introduction of Cal PB2 enhanced activity at 34°C, suggesting the presence of unidentified residues in Cal PB2 that are required for efficient growth at low temperature. Here, we sought to determine the key PB2 residues which confer enhanced polymerase activity and virus growth in human cells at low temperature. Using a reporter gene assay, we identified novel mutations, PB2 V661A and V683T/A684S, which are involved in enhanced Cal polymerase activity at low temperature. The PB2 T271A mutation, which we previously reported, also contributed to enhanced activity. The growth of recombinant Cal containing PB2 with Nan residues 271T/661V/683V/684A was strongly reduced in human cells compared to wild-type virus at low temperature. Among the four residues, 271A and 684S are conserved in human and pH1N1 viruses but not in avian viruses, suggesting an important role in mammalian adaptation of pH1N1 virus.IMPORTANCEThe PB2 protein plays a key role in the host adaptation, cold sensitivity, and pathogenesis of influenza A virus. Despite containing an avian origin PB2 lacking the mammalian adaptive mutations 627K or 701N, pH1N1 influenza virus strains can replicate efficiently in the low temperature upper respiratory tract of mammals, suggesting the presence of unknown mutations in the pH1N1 PB2 protein responsible for its low temperature adaptation. Here, in addition to PB2 271A, which has been shown to increase polymerase activity, we identified novel PB2 residues 661A and 683T/684S in pH1N1 which confer enhanced polymerase activity and virus growth in mammalian cells especially at low temperature. Our findings suggest that the presence of these PB2 residues contributes to efficient replication of the pH1N1 virus in the upper respiratory tract, which resulted in efficient human-to-human transmission of this virus.

scholarly journals Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

2011 ◽  
Vol 7 (12) ◽  
pp. e1002398 ◽  
Author(s):  
Rebecca M. DuBois ◽  
Hassan Zaraket ◽  
Muralidhar Reddivari ◽  
Richard J. Heath ◽  
Stephen W. White ◽  
...  
Keyword(s):  
Influenza Virus ◽  
H5n1 Influenza Virus ◽  
Acid Stability ◽  
H5n1 Influenza ◽  
Hemagglutinin Protein

scholarly journals Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies

2016 ◽  
Vol 22 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Haider Abdul-Lateef Mousa
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Influenza Viruses ◽  
Carnosic Acid ◽  
Upper Respiratory Tract ◽  
H5n1 Influenza ◽  
Prevention And Treatment ◽  
Upper Respiratory ◽  
Tract Infections ◽  
Viral Respiratory

In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.

scholarly journals Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in humans and ferrets

2018 ◽  
Author(s):  
Drishti Kaul ◽  
Raveen Rathnasinghe ◽  
Marcela Ferres ◽  
Gene S. Tan ◽  
Aldo Barrera ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cellular Damage ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Influenza A Virus Infection ◽  
Over Time

AbstractInfection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation because of host responses and cellular damage. The native upper respiratory tract (URT) microbiome likely plays a role, yet the effects of influenza infection on the URT microbiome are largely unknown. We performed a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes had stable “heathy ecostate” communities both within and between individuals. In contrast, infected patients and ferrets exhibited large changes in bacterial community composition over time and between individuals. The “unhealthy” ecostates of infected individuals progressed towards the “healthy ecostate” over time, coinciding with viral clearance and recovery. Blooms of Pseudomonas were a statistically associated constant in the disturbed microbiomes of infected individuals. The dynamic and resilient nature of the microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.One Sentence SummaryDynamics of the upper respiratory tract microbiome during influenza A virus infection

scholarly journals Innate Immune Responses to Influenza Virus Infections in the Upper Respiratory Tract

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2090
Author(s):  
Edin J. Mifsud ◽  
Miku Kuba ◽  
Ian G. Barr
Keyword(s):  
Influenza Virus ◽  
Immune System ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Innate Immune System ◽  
Innate Immune ◽  
Upper Respiratory Tract ◽  
Adaptive Immune ◽  
Upper Respiratory

The innate immune system is the host’s first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.

scholarly journals Reduction of Influenza Virus Titer and Protection against Influenza Virus Infection in Infant Mice Fed Lactobacillus casei Shirota

2004 ◽  
Vol 11 (4) ◽  
pp. 675-679 ◽  
Author(s):  
Hisako Yasui ◽  
Junko Kiyoshima ◽  
Tetsuji Hori
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Oral Administration ◽  
Lactobacillus Casei ◽  
Influenza Virus Infection ◽  
Interleukin 12 ◽  
Saline Control ◽  
Control Group ◽  
Upper Respiratory Tract ◽  
Upper Respiratory

ABSTRACT We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P < 0.05) lower than that in infant mice administered saline (control group) (102.48 ± 100.31 and 102.78 ± 100.4, respectively). Further, the survival rate of the L. casei Shirota group was significantly (P < 0.05) higher than that of the control group (14.3 versus 40.0%). One day after infection, pulmonary NK cell activity and interleukin-12 production by mediastinal lymph node cells of mice in the L. casei Shirota group were significantly greater than those of mice in the control group. These findings suggest that oral administration of L. casei Shirota activates the immature immune system of neonatal and infant mice and protects against IFV infection. Therefore, oral administration of L. casei Shirota may accelerate the innate immune response of the respiratory tract and protect against various respiratory infections in neonates, infants, and children, a high risk group for viral and bacterial infections.

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