Anti-influenza A virus restriction factors that shape the human species barrier and virus evolution

Petric, Philipp P.; Schwemmle, Martin; Graf, Laura

doi:10.1371/journal.ppat.1011450

Cited by 4 publications

(12 citation statements)

References 37 publications

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“…Arrayed expression screening of human (525) and macaque (345) ISGs on MT4 cells was performed, 1 and above‐mentioned cells were infected with Mallard‐GFP (an H1N1 avian strain), PR8‐GFP (a human laboratory‐adapted H1N1 strain), and Cal04 7:1 PR8 segment 8 GFP (a mouse‐adapted H1N1 strain). A series of host antiviral factors were identified, including previously reported ISGs, such as IFITM2, IFITM3, and Mx1 1,2,5 . Surprisingly, overexpression of BTN3A1 and BTN3A3 was found to restrict Mallard‐GFP rather than PR8‐GFP or maCal04‐GFP infection, implying that BTN3A3 specifically restricts avian IAVs 1 .…”

Section: Figurementioning

confidence: 91%

“…In particular, BTN3A3 is not the sole species barrier of zoonotic infections with IAVs 1 . As another molecular basis preventing spillover transmission of avian IAVs, Mx1 encodes myxovirus resistance protein A (MxA), which recognizes and blocks viral nucleoprotein from entering into the nucleus of infected cells 5 . The antiviral mechanism and sites of action are similar between BTN3A3 and Mx1, and their antiviral activity is exerted by inhibiting the transcription and replication of the viral genome at an early stage 2,5 .…”

Section: Figurementioning

confidence: 99%

“…1,2 Both residues 313 and 52 are situated on the surface of the nucleoprotein trimer and tightly arranged within the nucleoprotein head domain, implying that these two residues can interact with other viruses and host factors. 1,5 Immunohistochemistry found that the upper and lower respiratory tracts of healthy human donors both express BTN3A3 constitutively (Figure 1B), and type I or II IFNs can significantly upregulate BTN3A3 expression. Compared with the control group, overexpression of BTN3A3 potently protected C57BL/6 mice from pulmonary infection by Cal04 mutant (313F) but not Cal04 wild type (313 V).…”

mentioning

confidence: 91%

“…5 The antiviral mechanism and sites of action are similar between BTN3A3 and Mx1, and their antiviral activity is exerted by inhibiting the transcription and replication of the viral genome at an early stage. 2,5 However, both in vitro and in vivo data indicated that BTN3A3 and Mx1 exert their restrictive effects on IAV replication independently. 1,2 IAVs are enveloped negative-sense single-strand RNA viruses with eight RNA genomic segments, encoding RNA polymerase subunits, viral glycoproteins (hemagglutinin and neuraminidase), viral nucleoprotein, matrix protein (M1) and membrane protein (M2), the nonstructural protein NS1, and nuclear export protein.…”

mentioning

confidence: 99%

“…1,2 IAVs are enveloped negative-sense single-strand RNA viruses with eight RNA genomic segments, encoding RNA polymerase subunits, viral glycoproteins (hemagglutinin and neuraminidase), viral nucleoprotein, matrix protein (M1) and membrane protein (M2), the nonstructural protein NS1, and nuclear export protein. 3,5 To ascertain determining factors for the sensitivity to BTN3A3 in avian IAVs, the PR8/Mallard-IAV recombinant viruses with different fragments (7:1) were constructed and the plaque forming assay was used to measure the infectivity in Madin-Darby canine kidney (MDCK) cells overexpressing BTN3A3. Replacement of fragment 5 (nucleoprotein) in avian H1N1 with corresponding sequences of PR8 endowed the ability to escape from BTN3A3 restriction.…”

mentioning

confidence: 99%

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The determinants associated with zoonotic potential of influenza A viruses: BTN3A3 evasion mediated by residue mutation in the nucleoprotein

Tian,

Li,

Fan

2023

MedComm

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Section: Figurementioning

confidence: 91%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 91%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The determinants associated with zoonotic potential of influenza A viruses: BTN3A3 evasion mediated by residue mutation in the nucleoprotein

Tian,

Li,

Fan

2023

MedComm

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Mendelian randomization study on the causal effect of serum IgA levels on H7N9 avian influenza A virus susceptibility

Liao,

Shen,

Chen

et al. 2023

Journal of Medical Virology

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Avian influenza A viruses (IAVs) that cross the species barrier to infect humans have the potential to initiate a new pandemic. However, the host factors influencing avian IAV infection remain poorly understood. To address this knowledge gap, we conducted a two‐sample Mendelian randomization (MR) analysis by integrating our in‐house genome‐wide association study (GWAS) of avian IAV H7N9 susceptibility (with 217 cases and 116 controls) with the largest GWAS of serum IgA levels to date (sample size 41 263). Using the inverse‐variance weighted (IVW) method, we discovered that genetically decreased serum IgA levels were associated with an increased risk of H7N9 infection (β = −2.528, 95% confidence interval [CI]: −4.572 to −0.484; p = 0.015). Consistent results were obtained from three other MR methods, including robust IVW estimation (β = −2.506, 95% CI: −4.109 to −0.902; p = 0.002), generalized summary‐data‐based MR (GSMR) (β = −2.238, 95% CI: −4.106 to −0.602; p = 0.019), and MR‐pleiotropy residual sum and outlier (MR‐PRESSO) (β = −2.528, 95% CI: −4.396 to −0.892; p = 0.026). In conclusion, our analysis provided compelling evidence support a causal relationship between genetically predicted serum IgA levels and avian IAV H7N9 susceptibility.

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Influenza a virus antiparallel helical nucleocapsid-like pseudo-atomic structure

Chenavier,

Zarkadas,

Freslon

et al. 2024

Nucleic Acids Research

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Influenza A viruses are responsible for human seasonal epidemics and severe animal pandemics with a risk of zoonotic transmission to humans. The viral segmented RNA genome is encapsidated by nucleoproteins (NP) and attached to the heterotrimeric polymerase, forming the viral ribonucleoproteins (vRNPs). Flexible helical vRNPs are central for viral transcription and replication. In this study, we present an advanced biological tool, the antiparallel helical RNP-like complex, assembled from recombinant N-terminally truncated NP and short synthetic RNA. The 3.0 Å cryo-electron microscopy structure details for the first time the whole RNA pathway across NP as well as NP-NP interactions that drive the antiparallel helical assembly accommodating major and minor grooves. Our findings show that the surface of the protein can harbour several conformations of the RNA, confirming that the number of nucleobases that binds to NP is not fixed, but ranges probably between 20 and 24. Taking all together, our data provide details to further understand the genome encapsidation and explain the inherent flexibility of influenza A virus vRNPs.

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Anti-influenza A virus restriction factors that shape the human species barrier and virus evolution

Cited by 4 publications

References 37 publications

The determinants associated with zoonotic potential of influenza A viruses: BTN3A3 evasion mediated by residue mutation in the nucleoprotein

The determinants associated with zoonotic potential of influenza A viruses: BTN3A3 evasion mediated by residue mutation in the nucleoprotein

Mendelian randomization study on the causal effect of serum IgA levels on H7N9 avian influenza A virus susceptibility

Influenza a virus antiparallel helical nucleocapsid-like pseudo-atomic structure

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