Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 May:479-480:331-44.
doi: 10.1016/j.virol.2015.01.029. Epub 2015 Feb 18.

Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics

Christian K Pfaller  1 , Roberto Cattaneo  2 , Matthias J Schnell  3
Affiliations
Review

Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics

Christian K Pfaller et al. Virology. 2015 May.

Abstract

The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular basis of tissue tropism and pathogenesis. Studies have assessed the relevance for virulence of different receptors and the interactions with cellular proteins governing the innate immune responses. Research has also analyzed the mechanisms of attenuation. Based on these findings, ongoing clinical trials are exploring new live attenuated vaccines and the use of viruses re-engineered as cancer therapeutics.

Keywords: Attenuation; Cancer therapy; Innate immunity; Mononegavirales; Pathology; Receptors; Reverse genetics; Tropism; Vaccines.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Phylogeny of the genera within the order Mononegavirales. Genera for which reverse genetics systems have been established for at least one species are highlighted. The phylogenetic tree was generated with phyloT (Letunic and Bork, 2007, 2011). Abbreviations: B01 – Bornavirus; F01 – Cuevavirus; F02 – Ebolavirus; F03 – Marburgvirus; N01 – Nyavirus; P01 – Aquaparamyxovirus; P02 – Avulavirus; P03 – Ferlavirus; P04 – Henipavirus; P05 – Morbillivirus; P06 – Respirovirus; P07 – Rubulavirus; P08 – Metapneumovirus; P09 – Pneumovirus; R01 – Cytorhabdovirus; R02 – Ephemerovirus; R03 – Lyssavirus; R04 – Novirhabdovirus; R05 – Nucleorhabdovirus; R06 – Perhabdovirus; R07 – Sigmavirus; R08 – Sprivivirus; R09 – Tibrovirus; R10 – Tupavirus; R11 – Vesiculovirus.
Fig. 2
Fig. 2
General genome organization of Mononegaviruses. Size of the genomes and individual genes is proportional to their length.
Fig. 3
Fig. 3
Transcription and replication of a NNSV shown for RABV. (A) The encapsidated negative-strand RNA (yellow) serves as a template for the polymerase complex. Transcription starts with a short uncapped leader RNA (leRNA) from the 3′ end of the genomic RNA; this is followed by the transcription of 5′ capped and polyadenylated mRNAs, which encode the viral proteins (green). The polymerase complex stops at a signal sequence, ignores the intergenic region (IGR) and restarts transcription at the transcription start signal sequence. Subsequent attempts at transcription by the polymerase complex are not always successful; therefore, attenuation of transcription occurs in the direction of 3′-5′ (transcription gradient). (B) During replication, the polymerase complex ignores the transcription start/stop signals within the RABV genome (yellow), rendering a full-length antigenomic RNA (green), which is also encapsidated. The antigenomic RNA is encapsidated into the N protein along with the genomic RNA. The synthesized antigenome serves then as a template for the synthesis of additional copies of genomic RNA (yellow).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ammayappan A, Kurath G, Thompson TM, Vakharia VN. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity. Mar. Biotechnol. (NY) 2011;13:672–683. - PubMed
    1. Barber GN. VSV-tumor selective replication and protein translation. Oncogene. 2005;24:7710–7719. - PubMed
    1. Barik S, Banerjee AK. Sequential phosphorylation of the phosphoprotein of vesicular stomatitis virus by cellular and viral protein kinases is essential for transcription activation. J. Virol. 1992;66:1109–1118. - PMC - PubMed
    1. Baron MD, Barrett T. Rescue of rinderpest virus from cloned cDNA. J. Virol. 1997;71:1265–1271. - PMC - PubMed
    1. Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J. Virol. 2003;77:7945–7956. - PMC - PubMed

Publication types