Pseudotyping of vesicular stomatitis virus with the envelope glycoproteins of highly pathogenic avian influenza viruses

Zimmer, Gert; Locher, Samira; Rentsch, Marianne Berger; Halbherr, Stefan J.

doi:10.1099/vir.0.065201-0

Cited by 29 publications

(27 citation statements)

References 23 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A), indicating that the cells were actually fully polarized. When the cells were infected with VSV*ΔG-H5pb-N1, encoding HA and NA of a highly pathogenic avian H5N1 influenza virus (20), virus entry occurred from both sites. In contrast, VSV*ΔG-HL18bp entered polarized MDCK II cells predominantly from the basolateral membrane (Fig.…”

Section: Hl18 Mediates Infection Of Polarized Mdck II Cells From the mentioning

confidence: 99%

Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism

Moreira

Locher²,

Kolesnikova

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats and provisionally designated “HL17NL10” and “HL18NL11.” All efforts to isolate infectious virus from bats or to generate these viruses by reverse genetics have failed to date. Recombinant vesicular stomatitis virus (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 or HL18 in place of the VSV glycoprotein were generated to identify cell lines that are susceptible to bat influenza A-like virus entry. More than 30 cell lines derived from various species were screened but only a few cell lines were found to be susceptible, including Madin–Darby canine kidney type II (MDCK II) cells. The identification of cell lines susceptible to VSV chimeras allowed us to recover recombinant HL17NL10 and HL18NL11 viruses from synthetic DNA. Both influenza A-like viruses established a productive infection in MDCK II cells; however, HL18NL11 replicated more efficiently than HL17NL10 in this cell line. Unlike conventional influenza A viruses, bat influenza A-like viruses started the infection preferentially at the basolateral membrane of polarized MDCK II cells; however, similar to conventional influenza A viruses, bat influenza A-like viruses were released primarily from the apical site. The ability of HL18NL11 or HL17NL10 viruses to infect canine and human cells might reflect a zoonotic potential of these recently identified bat viruses.

show abstract

Section: Hl18 Mediates Infection Of Polarized Mdck II Cells From the mentioning

confidence: 99%

Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism

Moreira

Locher²,

Kolesnikova

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The resulting plasmids were designated pVSV*⌬G(NA) and pVSV*⌬G(HA), in which the asterisk denotes the presence of the eGFP gene and ⌬G indicates the absence of the glycoprotein G gene. For generation of pseudotype virus, a VSV vector backbone with 7 transcription units was used (52). The HA and NA genes of A/chicken/Yamaguchi/7/04 (H5N1) were inserted into the fourth and fifth transcription units, taking advantage of single MluI and XhoI restriction sites, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…In order to allow quantification of anti-NA-mediated inhibition of virus spread, we took advantage of a propagation-competent pseudotype virus expressing the HA and NA glycoproteins of highly pathogenic A/chicken/Yamaguchi/7/04 (H5N1) (52). The virus was further modified to express a secreted luciferase reporter protein (61) instead of the previously used green fluorescent protein (GFP) reporter (Fig.…”

Section: Na Antibodies Inhibit Virus Spread In Vitromentioning

confidence: 99%

Biological and Protective Properties of Immune Sera Directed to the Influenza Virus Neuraminidase

Halbherr¹,

Ludersdorfer²,

Ricklin³

et al. 2015

J Virol

Self Cite

View full text Add to dashboard Cite

The envelope of influenza A viruses contains two large antigens, hemagglutinin (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce neutralizing antibodies that are predominantly directed to the HA globular head, a domain that is subject to extensive antigenic drift. Antibodies directed to NA are induced at much lower levels, probably as a consequence of the immunodominance of the HA antigen. Although antibodies to NA may affect virus release by inhibiting the sialidase function of the glycoprotein, the antigen has been largely neglected in past vaccine design. In this study, we characterized the protective properties of monospecific immune sera that were generated by vaccination with recombinant RNA replicon particles encoding NA. These immune sera inhibited hemagglutination in an NA subtype-specific and HA subtype-independent manner and interfered with infection of MDCK cells. In addition, they inhibited the sialidase activities of various influenza viruses of the same and even different NA subtypes. With this, the anti-NA immune sera inhibited the spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped viruses in MDCK cells in a concentration-dependent manner. When chickens were immunized with NA recombinant replicon particles and subsequently infected with low-pathogenic avian influenza virus, inflammatory serum markers were significantly reduced and virus shedding was limited or eliminated. These findings suggest that NA antibodies can inhibit virus dissemination by interfering with both virus attachment and egress. Our results underline the potential of high-quality NA antibodies for controlling influenza virus replication and place emphasis on NA as a vaccine antigen. IMPORTANCEThe neuraminidase of influenza A viruses is a sialidase that acts as a receptor-destroying enzyme facilitating the release of progeny virus from infected cells. Here, we demonstrate that monospecific anti-NA immune sera inhibited not only sialidase activity, but also influenza virus hemagglutination and infection of MDCK cells, suggesting that NA antibodies can interfere with virus attachment. Inhibition of both processes, virus release and virus binding, may explain why NA antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA immune sera showed broader reactivity than anti-HA sera in hemagglutination inhibition tests and demonstrated cross-subtype activity in sialidase inhibition tests. These remarkable features of NA antibodies highlight the importance of the NA antigen for the development of next-generation influenza virus vaccines.

show abstract

“…Another group recently described the construction of replication-competent VSV⌬G recombinants expressing HA and NA (termed pseudotypes), but these were not tested in animals (60). As in our studies, the HA used in these hybrid VSVs was derived from a HPAIV strain containing a polybasic cleavage site.…”

Section: Discussionmentioning

confidence: 99%

A Viable Recombinant Rhabdovirus Lacking Its Glycoprotein Gene and Expressing Influenza Virus Hemagglutinin and Neuraminidase Is a Potent Influenza Vaccine

Ryder

Buonocore

Vogel

et al. 2015

J Virol

View full text Add to dashboard Cite

The emergence of novel influenza viruses that cause devastating human disease is an ongoing threat and serves as an impetus for the continued development of novel approaches to influenza vaccines. Influenza vaccine development has traditionally focused on producing humoral and/or cell-mediated immunity, often against the viral surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Here, we describe a new vaccine candidate that utilizes a replication-defective vesicular stomatitis virus (VSV) vector backbone that lacks the native G surface glycoprotein gene (VSV⌬G). The expression of the H5 HA of an H5N1 highly pathogenic avian influenza virus (HPAIV), A/Vietnam/1203/04 (VN1203), and the NA of the mouse-adapted H1N1 influenza virus A/Puerto Rico/8/34 (PR8) in the VSV⌬G vector restored the ability of the recombinant virus to replicate in cell culture, without the requirement for the addition of trypsin. We show here that this recombinant virus vaccine candidate was nonpathogenic in mice when given by either the intramuscular or intranasal route of immunization and that the in vivo replication of VSV⌬G-H5N1 is profoundly attenuated. This recombinant virus also provided protection against lethal H5N1 infection after a single dose. This novel approach to vaccination against HPAIVs may be widely applicable to other emerging strains of influenza virus. IMPORTANCEPreparation for a potentially catastrophic influenza pandemic requires novel influenza vaccines that are safe, can be produced and administered quickly, and are effective, both soon after administration and for a long duration. We have created a new influenza vaccine that utilizes an attenuated vesicular stomatitis virus (VSV) vector, to deliver and express influenza virus proteins against which vaccinated animals develop potent antibody responses. The influenza virus hemagglutinin and neuraminidase proteins, expressed on the surface of VSV particles, allowed this vaccine to grow in cell culture and induced a potent antibody response in mice that was effective against infection with a lethal influenza virus. The mice showed no adverse reactions to the vaccine, and they were protected against an otherwise lethal influenza infection after only 14 days postvaccination and after as many as 140 days postvaccination. The ability to rapidly produce this safe and effective vaccine in cell culture is additionally advantageous.

show abstract

Pseudotyping of vesicular stomatitis virus with the envelope glycoproteins of highly pathogenic avian influenza viruses

Cited by 29 publications

References 23 publications

Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism

Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism

Biological and Protective Properties of Immune Sera Directed to the Influenza Virus Neuraminidase

A Viable Recombinant Rhabdovirus Lacking Its Glycoprotein Gene and Expressing Influenza Virus Hemagglutinin and Neuraminidase Is a Potent Influenza Vaccine

Contact Info

Product

Resources

About