Limits...
Assessing the fitness of distinct clades of influenza A (H9N2) viruses.

- Emerg Microbes Infect (2013)

Bottom Line: Influenza A (H9N2) viruses are a genetically diverse population that infects wild and domestic avian species and mammals and contributed the internal gene segments to the A/H5N1 and A/H7N9 viruses associated with lethal human infections.However, the A/swine/Hong Kong/9A-1/1998 and A/chicken/Hong Kong/G9/1997 viruses also displayed several features suggesting a fitness profile adapted to human infection and transmission.Therefore, we conclude that comprehensive risk analyses based on surveillance of circulating influenza virus strains are necessary to assess the potential for human infection by emerging influenza A viruses.

View Article: PubMed Central - PubMed

ABSTRACT
Influenza A (H9N2) viruses are a genetically diverse population that infects wild and domestic avian species and mammals and contributed the internal gene segments to the A/H5N1 and A/H7N9 viruses associated with lethal human infections. Here we comprehensively assess the potential risk to mammals of a diverse panel of A/H9N2 viruses, representing the major H9N2 clades, using a combination of in vitro assays (e.g., antiviral susceptibility and virus growth in primary differentiated human airway cells) and in vivo assays (e.g., replication, transmission and/or pathogenicity of viruses in ducks, pigs, mice and ferrets). We observed that viruses isolated from humans, A/Hong Kong/1073/1999 and A/Hong Kong/33982/2009, had the highest risk potential. However, the A/swine/Hong Kong/9A-1/1998 and A/chicken/Hong Kong/G9/1997 viruses also displayed several features suggesting a fitness profile adapted to human infection and transmission. The North American avian H9N2 clade virus had the lowest risk profile, and the other viruses tested displayed various levels of fitness across individual assays. In many cases, the known genotypic polymorphisms alone were not sufficient to accurately predict the virus' phenotype. Therefore, we conclude that comprehensive risk analyses based on surveillance of circulating influenza virus strains are necessary to assess the potential for human infection by emerging influenza A viruses.

No MeSH data available.


Related in: MedlinePlus

Replication of H9N2 viruses in ferrets. Two ferrets each were intranasally inoculated with 106 TCID50 units of H9N2 virus of (A) human origin, (B) mammalian or avian origin or (C) avian origin. Brisbane/59 virus was used as a positive control. Viral titers in nasal washes were measured at 2, 4, 6 and 8 dpi. Each bar represents an individual ferret. The limit of detection was 10 TCID50/mL, and titers below that limit are shown at 0.5 log10 TCID50/mL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3924558&req=5

fig4: Replication of H9N2 viruses in ferrets. Two ferrets each were intranasally inoculated with 106 TCID50 units of H9N2 virus of (A) human origin, (B) mammalian or avian origin or (C) avian origin. Brisbane/59 virus was used as a positive control. Viral titers in nasal washes were measured at 2, 4, 6 and 8 dpi. Each bar represents an individual ferret. The limit of detection was 10 TCID50/mL, and titers below that limit are shown at 0.5 log10 TCID50/mL.

Mentions: To assess the ability of H9N2 viruses to replicate and transmit in ferrets, we intranasally inoculated three-month-old ferrets with 106 TCID50 of select H9N2 or A/Brisbane/59/2007 viruses (n=2 ferrets per group).We then assessed viral shedding in nasal washes at 2, 4, 6 and 8 dpi. Consistent with the efficient replication observed in NHBE cells, HK/33982 and HK/1073 viruses replicated to similar titers and kinetics as A/Brisbane/59/2007, the pre-pandemic seasonal H1N1 virus used as a positive control (Figure 4A). Similar replication efficiency and kinetics were observed with the swine/HK virus (Figure 4B). Surprisingly, many of the avian viruses, regardless of lineage, also replicated to similar titers and kinetics as the human-origin H9N2 and seasonal H1N1 viruses (Figure 4C). In fact, a subset of the avian-origin viruses (chicken/HK/G9, guinea fowl/HK, duck/Nanchang, chicken/Nanchang and chicken/HK/TP38) had 1–2 log10 TCID50/mL higher titers than did A/Brisbane/59/2007 at 6 dpi (Figure 4C). Only the shorebird/DE and quail/Bangl viruses replicated to titers that were significantly lower than that of the seasonal H1N1 virus and were cleared faster (Figures 4B and 4C).


Assessing the fitness of distinct clades of influenza A (H9N2) viruses.

- Emerg Microbes Infect (2013)

Replication of H9N2 viruses in ferrets. Two ferrets each were intranasally inoculated with 106 TCID50 units of H9N2 virus of (A) human origin, (B) mammalian or avian origin or (C) avian origin. Brisbane/59 virus was used as a positive control. Viral titers in nasal washes were measured at 2, 4, 6 and 8 dpi. Each bar represents an individual ferret. The limit of detection was 10 TCID50/mL, and titers below that limit are shown at 0.5 log10 TCID50/mL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924558&req=5

fig4: Replication of H9N2 viruses in ferrets. Two ferrets each were intranasally inoculated with 106 TCID50 units of H9N2 virus of (A) human origin, (B) mammalian or avian origin or (C) avian origin. Brisbane/59 virus was used as a positive control. Viral titers in nasal washes were measured at 2, 4, 6 and 8 dpi. Each bar represents an individual ferret. The limit of detection was 10 TCID50/mL, and titers below that limit are shown at 0.5 log10 TCID50/mL.
Mentions: To assess the ability of H9N2 viruses to replicate and transmit in ferrets, we intranasally inoculated three-month-old ferrets with 106 TCID50 of select H9N2 or A/Brisbane/59/2007 viruses (n=2 ferrets per group).We then assessed viral shedding in nasal washes at 2, 4, 6 and 8 dpi. Consistent with the efficient replication observed in NHBE cells, HK/33982 and HK/1073 viruses replicated to similar titers and kinetics as A/Brisbane/59/2007, the pre-pandemic seasonal H1N1 virus used as a positive control (Figure 4A). Similar replication efficiency and kinetics were observed with the swine/HK virus (Figure 4B). Surprisingly, many of the avian viruses, regardless of lineage, also replicated to similar titers and kinetics as the human-origin H9N2 and seasonal H1N1 viruses (Figure 4C). In fact, a subset of the avian-origin viruses (chicken/HK/G9, guinea fowl/HK, duck/Nanchang, chicken/Nanchang and chicken/HK/TP38) had 1–2 log10 TCID50/mL higher titers than did A/Brisbane/59/2007 at 6 dpi (Figure 4C). Only the shorebird/DE and quail/Bangl viruses replicated to titers that were significantly lower than that of the seasonal H1N1 virus and were cleared faster (Figures 4B and 4C).

Bottom Line: Influenza A (H9N2) viruses are a genetically diverse population that infects wild and domestic avian species and mammals and contributed the internal gene segments to the A/H5N1 and A/H7N9 viruses associated with lethal human infections.However, the A/swine/Hong Kong/9A-1/1998 and A/chicken/Hong Kong/G9/1997 viruses also displayed several features suggesting a fitness profile adapted to human infection and transmission.Therefore, we conclude that comprehensive risk analyses based on surveillance of circulating influenza virus strains are necessary to assess the potential for human infection by emerging influenza A viruses.

View Article: PubMed Central - PubMed

ABSTRACT
Influenza A (H9N2) viruses are a genetically diverse population that infects wild and domestic avian species and mammals and contributed the internal gene segments to the A/H5N1 and A/H7N9 viruses associated with lethal human infections. Here we comprehensively assess the potential risk to mammals of a diverse panel of A/H9N2 viruses, representing the major H9N2 clades, using a combination of in vitro assays (e.g., antiviral susceptibility and virus growth in primary differentiated human airway cells) and in vivo assays (e.g., replication, transmission and/or pathogenicity of viruses in ducks, pigs, mice and ferrets). We observed that viruses isolated from humans, A/Hong Kong/1073/1999 and A/Hong Kong/33982/2009, had the highest risk potential. However, the A/swine/Hong Kong/9A-1/1998 and A/chicken/Hong Kong/G9/1997 viruses also displayed several features suggesting a fitness profile adapted to human infection and transmission. The North American avian H9N2 clade virus had the lowest risk profile, and the other viruses tested displayed various levels of fitness across individual assays. In many cases, the known genotypic polymorphisms alone were not sufficient to accurately predict the virus' phenotype. Therefore, we conclude that comprehensive risk analyses based on surveillance of circulating influenza virus strains are necessary to assess the potential for human infection by emerging influenza A viruses.

No MeSH data available.


Related in: MedlinePlus