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RNAseq expression analysis of resistant and susceptible mice after influenza A virus infection identifies novel genes associated with virus replication and important for host resistance to infection.

Wilk E, Pandey AK, Leist SR, Hatesuer B, Preusse M, Pommerenke C, Wang J, Schughart K - BMC Genomics (2015)

Bottom Line: Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements.Using RNAseq analysis we identified novel genes important for viral replication or the host defense.This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany.

ABSTRACT

Background: The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection.

Results: We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection.

Conclusions: Using RNAseq analysis we identified novel genes important for viral replication or the host defense. This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.

No MeSH data available.


Related in: MedlinePlus

Expression levels of influenza genes. Normalized expression levels for influenza segments (PA, HA, M, NA, NS, PB1, PB2, NP) were calculated as mean expression values (log2 RPKM + 1), relative to respective mock treated animals (mock day 1 for day1 infected mice; mock day 3 for all other days p.i.). Lines represent expression levels from lungs of C57BL/6J at day 1, 3, 5, 8 and 14 p.i. (B6d1, B6d3, B6d5, B6d8, B6d14, respectively) and at day 1, 3, 5 p.i. for DBA/2J mice (D2d1, D2d3, D2d5, respectively). B6mock, D2mock: mock-treated C57BL/6J and DBA/2J control mice, respectively
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Fig2: Expression levels of influenza genes. Normalized expression levels for influenza segments (PA, HA, M, NA, NS, PB1, PB2, NP) were calculated as mean expression values (log2 RPKM + 1), relative to respective mock treated animals (mock day 1 for day1 infected mice; mock day 3 for all other days p.i.). Lines represent expression levels from lungs of C57BL/6J at day 1, 3, 5, 8 and 14 p.i. (B6d1, B6d3, B6d5, B6d8, B6d14, respectively) and at day 1, 3, 5 p.i. for DBA/2J mice (D2d1, D2d3, D2d5, respectively). B6mock, D2mock: mock-treated C57BL/6J and DBA/2J control mice, respectively

Mentions: In addition to expression profiling of host genes, RNAseq also allowed us to investigate transcripts of the eight viral segments. Expression levels of all influenza segments (calculated as RPKM: reads which map per kilobase of exon model per million mapped reads) changed in all infected mice over time and were highest at days 3 and 5 p.i. in C57BL/6J mice and at day 3 p.i. in DBA/2J mice (Fig. 2). In infected C57BL/6J mice, expression signals from influenza genes strongly decreased on day 8 p.i. and were at baseline levels of mock-treated controls on day 14 p.i. Expression levels of influenza transcripts were higher in DBA/2J mice compared to C57BL/6J mice at days 1 and 3 p.i. Most influenza RNA segments revealed a similar relative increase in expression, except for the segment encoding the neuraminidase (‘NA’) showing a lower increase compared to all other segments.Fig. 2


RNAseq expression analysis of resistant and susceptible mice after influenza A virus infection identifies novel genes associated with virus replication and important for host resistance to infection.

Wilk E, Pandey AK, Leist SR, Hatesuer B, Preusse M, Pommerenke C, Wang J, Schughart K - BMC Genomics (2015)

Expression levels of influenza genes. Normalized expression levels for influenza segments (PA, HA, M, NA, NS, PB1, PB2, NP) were calculated as mean expression values (log2 RPKM + 1), relative to respective mock treated animals (mock day 1 for day1 infected mice; mock day 3 for all other days p.i.). Lines represent expression levels from lungs of C57BL/6J at day 1, 3, 5, 8 and 14 p.i. (B6d1, B6d3, B6d5, B6d8, B6d14, respectively) and at day 1, 3, 5 p.i. for DBA/2J mice (D2d1, D2d3, D2d5, respectively). B6mock, D2mock: mock-treated C57BL/6J and DBA/2J control mice, respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4557482&req=5

Fig2: Expression levels of influenza genes. Normalized expression levels for influenza segments (PA, HA, M, NA, NS, PB1, PB2, NP) were calculated as mean expression values (log2 RPKM + 1), relative to respective mock treated animals (mock day 1 for day1 infected mice; mock day 3 for all other days p.i.). Lines represent expression levels from lungs of C57BL/6J at day 1, 3, 5, 8 and 14 p.i. (B6d1, B6d3, B6d5, B6d8, B6d14, respectively) and at day 1, 3, 5 p.i. for DBA/2J mice (D2d1, D2d3, D2d5, respectively). B6mock, D2mock: mock-treated C57BL/6J and DBA/2J control mice, respectively
Mentions: In addition to expression profiling of host genes, RNAseq also allowed us to investigate transcripts of the eight viral segments. Expression levels of all influenza segments (calculated as RPKM: reads which map per kilobase of exon model per million mapped reads) changed in all infected mice over time and were highest at days 3 and 5 p.i. in C57BL/6J mice and at day 3 p.i. in DBA/2J mice (Fig. 2). In infected C57BL/6J mice, expression signals from influenza genes strongly decreased on day 8 p.i. and were at baseline levels of mock-treated controls on day 14 p.i. Expression levels of influenza transcripts were higher in DBA/2J mice compared to C57BL/6J mice at days 1 and 3 p.i. Most influenza RNA segments revealed a similar relative increase in expression, except for the segment encoding the neuraminidase (‘NA’) showing a lower increase compared to all other segments.Fig. 2

Bottom Line: Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements.Using RNAseq analysis we identified novel genes important for viral replication or the host defense.This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany.

ABSTRACT

Background: The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection.

Results: We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection.

Conclusions: Using RNAseq analysis we identified novel genes important for viral replication or the host defense. This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.

No MeSH data available.


Related in: MedlinePlus