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Sequence analysis of measles virus hemagglutinin isolated in Argentina during the 1997-1998 outbreak
P R Barrero1, C D de Wolff, C A Passeggi
1Laboratory of Virology, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina.
Abstract:
Sequence analysis was performed on 50 measles viruses (MV) isolated in Argentina. Forty-six were obtained during the current outbreak (1997-1998), three from the previous outbreak (1991) and one sporadic case (1994). A 377-bp fragment of the hemagglutinin (H) gene was directly amplified by RT-PCR from nasopharyngeal secretions. Nucleotides 8152 to 8417 were sequenced and subjected to phylogenetic analysis. Multiple silent changes and point mutations were found in all MVs. In 1991, substitutions affected the third base in codons resulting in silent changes. In 1994 an A-->C substitution at position 8321 changed amino acids 351 (Leu-->Ile). In 1997-1998, an A-->G substitution at position 8339 changed amino acids 357 (Val-->Ile). In 3/46 viruses, guanine deletion at position 8205 changed the reading frame and insertion of an extra cytosine at nucleotide 8235 shifted it back to the original frame. Phylogenetic analysis revealed that viruses leading to the last two major outbreaks are clustered into two separate branches. MVs that prevailed until 1994 were related to genotype C1 and MVs of the current outbreak to D6. Random drift mutations rendered a 0.5 ratio of nonsilent over silent mutations in most of the MVs analyzed. However, in those showing a reading frame shift, the ratio was greater than 1, suggesting that it was driven by immune selection.
Insights
Sequence analysis of measles viruses (MV) in Argentina revealed distinct genetic lineages. Recent outbreaks (1997-1998) were linked to genotype D6, differing from earlier strains (genotype C1).
Area of Science:
- Virology
- Molecular Epidemiology
- Public Health
Background:
- Measles virus (MV) outbreaks pose a significant public health challenge.
- Understanding the genetic diversity of circulating MV strains is crucial for effective control strategies.
Purpose of the Study:
- To analyze the genetic sequences of measles viruses isolated in Argentina.
- To identify the genotypes and evolutionary patterns of MV strains responsible for recent outbreaks.
Main Methods:
- Direct amplification of a hemagglutinin (H) gene fragment using RT-PCR from nasopharyngeal secretions.
- Sequencing of a 377-bp fragment (nucleotides 8152-8417).
- Phylogenetic analysis to determine MV genotypes and evolutionary relationships.
Main Results:
- Analysis of 50 MV isolates (1991-1998) revealed multiple mutations, including silent changes and amino acid substitutions.
- Phylogenetic analysis identified two distinct MV lineages: genotype C1 (prevailing until 1994) and genotype D6 (associated with the 1997-1998 outbreak).
- Viruses with reading frame shifts exhibited a higher ratio of nonsilent to silent mutations, suggesting immune selection pressure.
Conclusions:
- Argentine measles virus outbreaks are driven by distinct genetic lineages.
- The shift from genotype C1 to D6 highlights the dynamic evolution of MV.
- Evidence suggests immune selection may play a role in MV evolution, particularly in strains with altered reading frames.