Faculty Opinions recommendation of Transcriptional silencing of geminiviral promoter-driven transgenes following homologous virus infection.

ABSTRACTInfluenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus.

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Post-exposure treatment with whole inactivated H5N1 avian influenza virus protects against lethal homologous virus infection in mice

Scientific Reports ◽

10.1038/srep29433 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 2

Author(s):

Mable Hagan ◽

Charlene Ranadheera ◽

Jonathan Audet ◽

Jocelyn Morin ◽

Anders Leung ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Exposure Treatment ◽

H5n1 Avian Influenza Virus ◽

Post Exposure ◽

H5n1 Avian Influenza ◽

Homologous Virus

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Protection and antibody responses in different strains of mouse immunized with plasmid DNAs encoding influenza virus haemagglutinin, neuraminidase and nucleoprotein

Journal of General Virology ◽

10.1099/0022-1317-80-10-2559 ◽

1999 ◽

Vol 80 (10) ◽

pp. 2559-2564 ◽

Cited By ~ 73

Author(s):

Ze Chen ◽

Tomoki Yoshikawa ◽

Shin-etsu Kadowaki ◽

Yukari Hagiwara ◽

Kazutoshi Matsuo ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Lethal Dose ◽

Serum Antibody ◽

Influenza Virus Infection ◽

Antibody Responses ◽

Significant Protection ◽

Plasmid Dnas ◽

Homologous Virus ◽

Different Strains

Protection against influenza virus infection and antibody responses in mice vaccinated with plasmid DNAs encoding haemagglutinin (HA), neuraminidase (NA) and nucleoprotein (NP) were compared among BALB/c (H-2d), B10 (H-2b) and C3H (H-2k ) mice. Mice were inoculated with each DNA construct twice, 3 weeks apart, at a dose of 1 μg per mouse by particle-mediated DNA transfer (gene gun) to the epidermis. They were challenged with a lethal dose of the homologous virus 7 days after the second vaccination. NA-DNA provided significant protection in all strains of mouse, whereas HA-DNA afforded significant protection only in BALB/c mice. The serum antibody titres against NA or HA molecules in BALB/c, C3H and B10 mice were high, intermediate and low, respectively. NP-DNA failed to provide protection in any strain of mouse, and elicited low titres of anti-NP antibodies. These results suggest that NA-DNA can be used as a vaccine component to provide effective protection against influenza virus infection in various strains of mouse.

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A rhesus macaque model of Asia lineage Zika virus infection

10.1101/046334 ◽

2016 ◽

Cited By ~ 2

Author(s):

Dawn M. Dudley ◽

Matthew T. Aliota ◽

Emma Mohr ◽

Andrea M. Weiler ◽

Gabrielle Lehrer-Brey ◽

...

Keyword(s):

T Cells ◽

Virus Infection ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Rhesus Macaques ◽

Case Reports ◽

Viral Rna ◽

Zika Virus Infection ◽

Homologous Virus ◽

Asian Lineage

Infection with Asian lineage Zika virus has been associated with Guillain-Barré syndrome and fetal abnormalities1–4, but the mechanisms and risk factors for these outcomes remain unknown. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage virus closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, Zika virus RNA was detected in plasma one day post-infection (dpi) in all animals (N = 8, including 2 animals infected during the first trimester of pregnancy). Plasma viral loads peaked above 1 × 105viral RNA copies/mL in seven of eight animals. Viral RNA was also present in saliva, urine, and cerebrospinal fluid (CSF), consistent with case reports from infected humans. Viral RNA was cleared from plasma and urine by 21 dpi in non-pregnant animals. In contrast, both pregnant animals remained viremic longer, up to 57 days. In all animals, infection was associated with transient increases in proliferating natural killer cells, CD8+ T cells, CD4+ T cells, and plasmablasts. Neutralizing antibodies were detected in all animals by 21 dpi. Rechallenge of three non-pregnant animals with the Asian-lineage Zika virus 10 weeks after the initial challenge resulted in no detectable virus replication, suggesting that primary Zika virus infection elicits protective immunity against homologous virus strains. These data establish that Asian-lineage Zika virus infection of rhesus macaques provides a relevant animal model for studying pathogenesis in pregnant and non-pregnant individuals and evaluating potential interventions against human infection, including during pregnancy.

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A Live Attenuated Human Metapneumovirus Vaccine Strain Provides Complete Protection against Homologous Viral Infection and Cross-Protection against Heterologous Viral Infection in BALB/c Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00145-13 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1246-1254 ◽

Cited By ~ 15

Author(s):

Ping Liu ◽

Zhou Shu ◽

Xian Qin ◽

Ying Dou ◽

Yao Zhao ◽

...

Keyword(s):

Virus Infection ◽

Viral Infection ◽

Vaccine Strain ◽

Human Metapneumovirus ◽

Cross Protection ◽

Wild Type Virus ◽

Complete Protection ◽

F Protein ◽

Homologous Virus ◽

Heterologous Virus

ABSTRACTA live attenuated vaccine candidate strain (M2) of human metapneumovirus (hMPV) was generated by removing the N-linked carbohydrate at amino acid 172 in the fusion (F) protein. Previously, replication of M2 in mouse lungs could be detected by molecular assays but not by viral titration. In the present study, the protective effects of M2 against infection by homologous or heterologous viruses were evaluated in BALB/c mice. Immunization with M2 produced a high titer of serum virus-neutralizing antibodies in BALB/c mice at 4 and 8 weeks postimmunization, with the titers against the homologous virus being higher than those against the heterologous virus. Challenges at 4 and 8 weeks postinoculation with M2 or wild-type virus led to no replication when mice were challenged with a homologous virus and extremely reduced replication when mice were challenged with a heterologous virus, as determined by the detection of viral genomic RNA copies in the lungs, as well as significantly milder pulmonary pathology. Thus, M2, with only one N-linked carbohydrate removed in the F protein, provides complete protection from homologous virus infection and substantial cross-protection from heterologous virus infection for at least 56 days after inoculation. This vaccine strain may therefore be a candidate for further preclinical study. Furthermore, this attenuating strategy (changing the glycosylation of a major viral protein) may be useful in the development of other viral vaccines.

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Immunity to influenza in ferrets V. Immunization with inactivated virus in adjuvant 65

Journal of Hygiene ◽

10.1017/s0022172400046258 ◽

1973 ◽

Vol 71 (1) ◽

pp. 97-106 ◽

Cited By ~ 9

Author(s):

C. W. Potter ◽

C. McLaren ◽

S. L. Shore

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Virus Infection ◽

Serum Antibody ◽

Temperature Response ◽

Neutralizing Antibody ◽

Febrile Reaction ◽

Challenge Virus ◽

Homologous Virus ◽

Detectable Serum

SUMMARYFerrets infected with influenza virus A2/Hong Kong/3/68 responded with a febrile reaction; the temperature was elevated by 1·0°C. or greater to a level of 40°C. or more. In addition, relatively high titres of virus were recovered from nasal washings taken 3 days after virus infection, serum antibody was produced, increased nasal protein was detected and nasal washings contained both HI and neutralizing antibody. Of four ferrets immunized with 400 CCA units of inactivated influenza virus A2/Aichi/2/68 in saline, only one produced detectable serum HI antibody, and none produced detectable nasal antibody. These ferrets were subsequently found to be susceptible to intranasal infection with influenza virus A2/Hong Kong/3/68. Thus, the temperature response, the titre of virus recovered from nasal washings and the serum HI antibody response found after virus infection was similar to that found after infection of non-immunized ferrets. However, the increase in protein concentration and the titre of HI and neutralizing antibody found in nasal washings after virus infection was detectably less than that found after virus infection of non-immunized ferrets.Four ferrets were immunized with 400 CCA units of inactivated A2/Aichi/2/68 virus in adjuvant 65, and these ferrets produced relatively high titres of serum HI antibody but no detectable nasal antibody. After subsequent virus infection with influenza virus A2/Hong Kong/3/68, these ferrets showed a modified temperature response, reduced titres of virus in nasal washings compared to that found in nasal washings from non-immunized ferrets, no increase in nasal protein and no detectable nasal HI antibody. Thus, immunization with inactivated virus in adjuvant 65 resulted in a significant modification of the response of ferrets to challenge virus; however, the immunity was not complete, and appreciably less than that found after infection with live homologous virus.

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Transcriptional Silencing of Geminiviral Promoter-Driven Transgenes Following Homologous Virus Infection

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi.2003.16.5.429 ◽

2003 ◽

Vol 16 (5) ◽

pp. 429-438 ◽

Cited By ~ 45

Author(s):

Mark Seemanpillai ◽

Ian Dry ◽

John Randles ◽

Ali Rezaian

Keyword(s):

Virus Infection ◽

Transgene Expression ◽

Transgene Silencing ◽

Specific Expression ◽

Floral Tissue ◽

Promoter Sequences ◽

Deacetylase Inhibitor ◽

Homologous Virus ◽

Tomato Leaf Curl ◽

Leaf Curl Virus

Promoters isolated from the Tomato leaf curl virus (TLCV) drive both constitutive and tissue-specific expression in transgenic tobacco. Following systemic TLCV infection of plants stably expressing TLCV promoter:GUS transgenes, transgene expression driven by all six TLCV promoters was silenced. Silencing in the TLCV coat protein promoter:GUS plants (V2:GUSΔC) was characterized in more detail. Transgene silencing observed in leaf, stem, and preanthesis floral tissue occurred with the continued replication of TLCV in host tissues. Infection of the V2:GUSΔC plants with heterologous geminiviruses did not result in transgene silencing, indicating that silencing was specifically associated with TLCV infection. Nuclear run-on assays indicated that silencing was due to the abolition of transcription from the V2:GUSΔC transgene. Bisulfite sequencing showed that silencing was associated with cytosine hypermethylation of the TLCV-derived promoter sequences of the V2:GUSΔC transgene. Progeny derived from V2:GUSΔC plants silenced by TLCV infection were analyzed. Transgene expression was silenced in progeny seedlings but was partially reactivated in the majority of plants by 75 days postgermination. Progeny seedlings treated with the nonmethylatable cytosine analog 5-azacytidine or the histone deacetylase inhibitor sodium butyrate exhibited partial reactivation of expression. This is the first report of the hypermethylation of a virus-derived transgene associated with a DNA virus infection.

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