The first genetic characterization of a D4 measles virus strain derived from a patient with subacute sclerosing panencephalitis

BackgroundThe canonical genome organization of measles virus (MV) is characterized by total size of 15 894 nucleotides (nts) and defined length of every genomic region, both coding and non-coding. Only rarely have reports of strains possessing non-canonical genomic properties (possessing indels, with or without the change of total genome length) been published. The observed mutations are mutually compensatory in a sense that the total genome length remains polyhexameric. Although programmed and highly precise pseudo-templated nucleotide additions during transcription are inherent to polymerases of all viruses belonging to family Paramyxoviridae, a similar mechanism that would serve to non-randomly correct genome length, if an indel has occurred during replication, has so far not been described in the context of a complete virus genome.MethodsWe compiled all complete MV genomic sequences (64 in total) available in open access sequence databases. Multiple sequence comparisons and phylogenetic analyses were performed with the aim of exploring whether non-recombinant and non-evolutionary linked measles strains that show deviations from canonical genome organization possess a common genetic characteristic.ResultsIn 11 MV sequences we detected deviations from canonical genome organization due to short indels located within homopolymeric stretches or next to them. In nine out of 11 identified non-canonical MV sequences, a common feature was observed: one mutation, either an insertion or a deletion, was located in a 28 nts long region in F gene 5′ untranslated region (positions 5051–5078 in genomic cDNA of canonical strains). This segment is composed of five tandemly linked homopolymeric stretches, its consensus sequence is G6-7C7-8A6-7G1-3C5-6. Although none of the mononucleotide repeats within this segment has fixed length, the total number of nts in canonical strains is always 28. These nine non-canonical strains, as well as the tenth (not mutated in 5051–5078 segment), can be grouped in three clusters, based on their passage histories/epidemiological data/genetic similarities. There are no indications that the 3 clusters are evolutionary linked, other than the fact that they all belong to clade D.ConclusionsA common narrow genomic region was found to be mutated in different, non-related, wild type strains suggesting that this region might have a function in non-random genome length corrections occurring during MV replication.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0587-2) contains supplementary material, which is available to authorized users.

show abstract

“…Isolation of MVi/Zagreb.CRO/48.03[D4] and MVi/Zagreb.CRO/19.08[D4] viruses was described in Ivancic-Jelecki et al [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Common position of indels that cause deviations from canonical genome organization in different measles virus strains

Ivancic-Jelecki

Slović

Šantak

et al. 2016

Virol J

Self Cite

View full text Add to dashboard Cite

show abstract

“…The genotype that is detected in persistently infected brain tissues is usually consistent with the genotype that was circulating at the time when the patient experienced acute measles infection. However, to our knowledge, viruses belonging to only 10 different genotypes have been isolated from SSPE patients (A, B, C1, C2, D1, D3, D4, D5, D7, E and F), while only three genotypes have been found in MIBE patients (A, B3 and E) [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. That the latter occurs exclusively in immunocompromised subjects may explain that a vaccine strain (genotype A) [ 13 ] has been found to be the cause of at least one case of MIBE, whereas vaccine strains of measles have not been isolated in any cases of SSPE [ 20 ].…”

Section: Genotypic Heterogeneity In Measles Virusmentioning

confidence: 96%

Constraints on the Genetic and Antigenic Variability of Measles Virus

Beaty

Lee

2016

Viruses

View full text Add to dashboard Cite

Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.

show abstract

“…These hypermutations are known to play an important role in the glycoprotein interaction and to hamper the ability of measles virus strain to produce cell-free infectious viral particles, and ultimately incorporated in the maintenance of persistent infection, disease development, and fulminant escalation. [2][3][4][5] Moreover, no genome sequences of measles vaccine strains were detected from SSPE cases. [2][3][4][5] I presume that a similar molecular characterization of the whole genome of MV in the studied patient was envisaged.…”

Section: Fulminant Subacute Sclerosing Panencephalitis In An Immunizementioning

confidence: 99%

“…[2][3][4][5] Moreover, no genome sequences of measles vaccine strains were detected from SSPE cases. [2][3][4][5] I presume that a similar molecular characterization of the whole genome of MV in the studied patient was envisaged. I presume that the task could not be contemplated probably due to financial constraints.…”

Section: Fulminant Subacute Sclerosing Panencephalitis In An Immunizementioning

confidence: 99%

Fulminant subacute sclerosing panencephalitis in an immunized 20-month-old Indian boy

Al-Mendalaw¹,

Kaushik²

2019

Neurosciences

View full text Add to dashboard Cite

The first genetic characterization of a D4 measles virus strain derived from a patient with subacute sclerosing panencephalitis

Cited by 5 publications

References 61 publications

Common position of indels that cause deviations from canonical genome organization in different measles virus strains

Common position of indels that cause deviations from canonical genome organization in different measles virus strains

Constraints on the Genetic and Antigenic Variability of Measles Virus

Fulminant subacute sclerosing panencephalitis in an immunized 20-month-old Indian boy

Contact Info

Product

Resources

About