scholarly journals Weak cis and trans Interactions of the Hemagglutinin with Receptors Trigger Fusion Proteins of Neuropathogenic Measles Virus Isolates

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Yuta Shirogane ◽  
Takao Hashiguchi ◽  
Yusuke Yanagi
Keyword(s):  
Membrane Fusion ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Target Cells ◽  
Wild Type ◽  
F Protein ◽  
The Brain ◽  
H Protein ◽  
In Cells ◽  
Cell Cell

ABSTRACT Measles virus (MeV) is an enveloped RNA virus bearing two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. Upon receptor binding, the H protein triggers conformational changes of the F protein, causing membrane fusion and subsequent virus entry. MeV may persist in the brain, infecting neurons and causing fatal subacute sclerosing panencephalitis (SSPE). Since neurons do not express either of the MeV receptors, signaling lymphocytic activation molecule (SLAM; also called CD150) and nectin-4, how MeV propagates in neurons is unknown. Recent studies have shown that specific substitutions in the F protein found in MeV isolates from SSPE patients are critical for MeV neuropathogenicity by rendering the protein unstable and hyperfusogenic. Recombinant MeVs possessing the F proteins with such substitutions can spread in primary human neurons and in the brains of mice and hamsters and induce cell-cell fusion in cells lacking SLAM and nectin-4. Here, we show that receptor-blind mutant H proteins that have decreased binding affinities to receptors can support membrane fusion mediated by hyperfusogenic mutant F proteins, but not the wild-type F protein, in cells expressing the corresponding receptors. The results suggest that weak interactions of the H protein with certain molecules (putative neuron receptors) trigger hyperfusogenic F proteins in SSPE patients. Notably, where cell-cell contacts are ensured, the weak cis interaction of the H protein with SLAM on the same cell surface also could trigger hyperfusogenic F proteins. Some enveloped viruses may exploit such cis interactions with receptors to infect target cells, especially in cell-to-cell transmission. IMPORTANCE Measles virus (MeV) may persist in the brain, causing incurable subacute sclerosing panencephalitis (SSPE). Because neurons, the main target in SSPE, do not express receptors for wild-type (WT) MeV, how MeV propagates in the brain is a key question for the disease. Recent studies have demonstrated that specific substitutions in the MeV fusion (F) protein are critical for neuropathogenicity. Here, we show that weak cis and trans interactions of the MeV attachment protein with receptors that are not sufficient to trigger the WT MeV F protein can trigger the mutant F proteins from neuropathogenic MeV isolates. Our study not only provides an important clue to understand MeV neuropathogenicity but also reveals a novel viral strategy to expand cell tropism.

Short-stalk isoforms of CADM1 and CADM2 trigger neuropathogenic measles virus-mediated membrane fusion by interacting with the viral hemagglutinin

2021 ◽  
Author(s):  
Ryuichi Takemoto ◽  
Tateki Suzuki ◽  
Takao Hashiguchi ◽  
Yusuke Yanagi ◽  
Yuta Shirogane
Keyword(s):  
Cell Membrane ◽  
Membrane Fusion ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Febrile Illness ◽  
Host Factors ◽  
F Protein ◽  
Short Stalk ◽  
Head Domain ◽  
H Protein

Measles virus (MeV), an enveloped RNA virus in the family Paramyxoviridae , usually causes acute febrile illness with skin rash, but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). MeV bears two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. The H protein possesses a head domain that initially mediates receptor binding and a stalk domain that subsequently transmits the fusion-triggering signal to the F protein. We have recently shown that cell adhesion molecule 1 (CADM1, also known as IGSF4A, Necl-2, SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, SynCAM2) are host factors enabling cell-cell membrane fusion mediated by hyperfusogenic F proteins of neuropathogenic MeVs as well as MeV spread between neurons lacking the known receptors. CADM1 and CADM2 interact in cis with the H protein on the same cell membrane, triggering hyperfusogenic F protein-mediated membrane fusion. Multiple isoforms of CADM1 and CADM2 containing various lengths of their stalk regions are generated by alternative splicing. Here we show that only short-stalk isoforms of CADM1 and CADM2 predominantly expressed in the brain induce hyperfusogenic F protein-mediated membrane fusion. While the known receptors interact in trans with the H protein through its head domain, these isoforms can interact in cis even with the H protein lacking the head domain and trigger membrane fusion, presumably through its stalk domain. Thus, our results unveil a new mechanism of viral fusion triggering by host factors. Importance Measles, an acute febrile illness with skin rash, is still an important cause of childhood morbidity and mortality worldwide. Measles virus (MeV), the causative agent of measles, may also cause a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. The disease is fatal, and no effective therapy is available. Recently, we have reported that cell adhesion molecule 1 (CADM1) and CADM2 are host factors enabling MeV cell-to-cell spread in neurons. These molecules interact in cis with the MeV attachment protein on the same cell membrane, triggering the fusion protein and causing membrane fusion. CADM1 and CADM2 are known to exist in multiple splice isoforms. In this study, we report that their short-stalk isoforms can induce membrane fusion by interacting in cis with the viral attachment protein independently of its receptor-binding head domain. This finding may have important implications for cis -acting fusion triggering by host factors.

scholarly journals Previously Unrecognized Amino Acid Substitutions in the Hemagglutinin and Fusion Proteins of Measles Virus Modulate Cell-Cell Fusion, Hemadsorption, Virus Growth, and Penetration Rate

2009 ◽  
Vol 83 (17) ◽  
pp. 8713-8721 ◽  
Author(s):  
Hiromi Okada ◽  
Masae Itoh ◽  
Kyosuke Nagata ◽  
Kaoru Takeuchi
Keyword(s):  
Amino Acid ◽  
Cell Fusion ◽  
Measles Virus ◽  
Vero Cells ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Virus Growth ◽  
F Protein ◽  
H Protein ◽  
Cell Cell

ABSTRACT Wild-type measles virus (MV) isolated in B95a cells could be adapted to Vero cells after several blind passages. In this study, we have determined the complete nucleotide sequences of the genomes of the wild type (T11wild) and its Vero cell-adapted (T11Ve-23) MV strain and identified amino acid substitutions R516G, E271K, D439E and G464W (D439E/G464W), N481Y/H495R, and Y187H/L204F in the nucleocapsid, V, fusion (F), hemagglutinin (H), and large proteins, respectively. Expression of mutated H and F proteins from cDNA revealed that the H495R substitution, in addition to N481Y, in the H protein was necessary for the wild-type H protein to use CD46 efficiently as a receptor and that the G464W substitution in the F protein was important for enhanced cell-cell fusion. Recombinant wild-type MV strains harboring the F protein with the mutations D439E/G464W [F(D439E/G464W)] and/or H(N481Y/H495R) protein revealed that both mutated F and H proteins were required for efficient syncytium formation and virus growth in Vero cells. Interestingly, a recombinant wild-type MV strain harboring the H(N481Y/H495R) protein penetrated slowly into Vero cells, while a recombinant wild-type MV strain harboring both the F(D439E/G464W) and H(N481Y/H495R) proteins penetrated efficiently into Vero cells, indicating that the F(D439E/G464W) protein compensates for the inefficient penetration of a wild-type MV strain harboring the H(N481Y/H495R) protein. Thus, the F and H proteins synergistically function to ensure efficient wild-type MV growth in Vero cells.

scholarly journals Cell-to-Cell Measles Virus Spread between Human Neurons Is Dependent on Hemagglutinin and Hyperfusogenic Fusion Protein

2018 ◽  
Vol 92 (6) ◽  
Author(s):  
Yuma Sato ◽  
Shumpei Watanabe ◽  
Yoshinari Fukuda ◽  
Takao Hashiguchi ◽  
Yusuke Yanagi ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Acute Infection ◽  
Syncytium Formation ◽  
Wild Type ◽  
F Protein ◽  
Human Neurons ◽  
A Cell ◽  
Nt2 Neurons

ABSTRACTMeasles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusion-enhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4-dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV.IMPORTANCEMeasles virus (MV), in rare cases, persists in the human central nervous system (CNS) and causes subacute sclerosing panencephalitis (SSPE) several years after acute infection. This neurological complication is almost always fatal, and there is currently no effective treatment for it. Mechanisms by which MV invades the CNS and causes the disease remain to be elucidated. We have previously shown that fusion-enhancing substitutions in the fusion protein of MVs isolated from SSPE patients contribute to MV spread in neurons. In this study, we demonstrate that MV bearing the hyperfusogenic mutant fusion protein spreads between human neurons in a cell-to-cell manner. Spread of the virus was inhibited by a fusion inhibitor peptide and antibodies against the MV hemagglutinin, indicating that both the hemagglutinin and hyperfusogenic fusion protein play important roles in MV spread between human neurons. The findings help us better understand the disease process of SSPE.

scholarly journals CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells

2010 ◽  
Vol 84 (9) ◽  
pp. 4183-4193 ◽  
Author(s):  
Akira Watanabe ◽  
Misako Yoneda ◽  
Fusako Ikeda ◽  
Yuri Terao-Muto ◽  
Hiroki Sato ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Neuronal Cells ◽  
Wild Type ◽  
Cyclophilin B ◽  
Transmembrane Glycoprotein ◽  
Signaling Lymphocytic Activation Molecule ◽  
Entry Receptor ◽  
H Protein

ABSTRACT Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions.

scholarly journals Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Fabrizio Angius ◽  
Heidi Smuts ◽  
Ksenia Rybkina ◽  
Debora Stelitano ◽  
Brian Eley ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Neurological Complications ◽  
Neural Cells ◽  
Viral Receptor ◽  
Tissue Samples ◽  
F Protein ◽  
Recombinant Viruses ◽  
The Brain

ABSTRACTDuring a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analyzed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein, MeV H, in order to fuse, MIBE F did not. Both F proteins had decreased thermal stability compared to that of the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain.IMPORTANCEMeasles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is associated with infection of the brain. We also demonstrate that hyperfusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells.

scholarly journals Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Hasan Kweder ◽  
Michelle Ainouze ◽  
Joanna Brunel ◽  
Denis Gerlier ◽  
Evelyne Manet ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
M Protein ◽  
Wild Type ◽  
Virus Identification ◽  
Viral Spread ◽  
M Proteins ◽  
Children And Young Adults ◽  
The Brain

Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.

scholarly journals The F Gene of the Osaka-2 Strain of Measles Virus Derived from a Case of Subacute Sclerosing Panencephalitis Is a Major Determinant of Neurovirulence

2010 ◽  
Vol 84 (21) ◽  
pp. 11189-11199 ◽  
Author(s):  
Minoru Ayata ◽  
Kaoru Takeuchi ◽  
Makoto Takeda ◽  
Shinji Ohgimoto ◽  
Seiichi Kato ◽  
...  
Keyword(s):  
Recombinant Virus ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Syncytium Formation ◽  
Vero Cells ◽  
Wild Type ◽  
M Gene ◽  
Hamster Model ◽  
F Protein ◽  
F Gene

ABSTRACT Measles virus (MV) is the causative agent for acute measles and subacute sclerosing panencephalitis (SSPE). Although numerous mutations have been found in the MV genome of SSPE strains, the mutations responsible for the neurovirulence have not been determined. We previously reported that the SSPE Osaka-2 strain but not the wild-type strains of MV induced acute encephalopathy when they were inoculated intracerebrally into 3-week-old hamsters. The recombinant MV system was adapted for the current study to identify the gene(s) responsible for neurovirulence in our hamster model. Recombinant viruses that contained envelope-associated genes from the Osaka-2 strain were generated on the IC323 wild-type MV background. The recombinant virus containing the M gene alone did not induce neurological disease, whereas the H gene partially contributed to neurovirulence. In sharp contrast, the recombinant virus containing the F gene alone induced lethal encephalopathy. This phenotype was related to the ability of the F protein to induce syncytium formation in Vero cells. Further study indicated that a single T461I substitution in the F protein was sufficient to transform the nonneuropathogenic wild-type MV into a lethal virus for hamsters.

scholarly journals Depletion of measles virus glycoprotein-specific antibodies from human sera reveals genotype-specific neutralizing antibodies

2009 ◽  
Vol 90 (12) ◽  
pp. 2982-2989 ◽  
Author(s):  
Rik L. de Swart ◽  
Selma Yüksel ◽  
Carianne N. Langerijs ◽  
Claude P. Muller ◽  
Albert D. M. E. Osterhaus
Keyword(s):  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Complete Elimination ◽  
Wild Type ◽  
Specific Antibodies ◽  
F Protein ◽  
Virus Glycoprotein ◽  
Measles Outbreak ◽  
Human Sera ◽  
H Protein

Measles virus (MV)-neutralizing antibodies in sera from vaccinated subjects are mainly directed against the haemagglutinin (H) protein. It has been shown previously that depletion of vaccination-induced H-specific antibodies by co-culture of sera with cells expressing the MV Edmonston strain H glycoprotein resulted in almost complete elimination of neutralizing activity. In the present study, MV H and/or fusion (F) protein-specific antibodies were depleted from sera of naturally immune subjects. Early convalescent samples were collected 1.5 years after a well-characterized measles outbreak in Luxembourg caused by a genotype C2 virus, whilst late convalescent samples were collected from healthy Dutch subjects born between 1960 and 1970. Depletion of both H- and F-specific antibodies completely eliminated virus-neutralizing (VN) activity against MV Edmonston. However, in the early convalescent samples, residual VN antibody against wild-type MV genotype C2 was detected. This demonstrated that, although the majority of MV-specific VN antibodies recognized epitopes conserved between different genotypes, genotype-specific VN epitopes were also induced. In sera depleted of H-specific antibodies only, VN activity against MV Edmonston was not completely eliminated, demonstrating the presence of F-specific VN antibodies. In conclusion, this study demonstrated that a fraction of VN antibodies induced by wild-type MV genotype C2 does not neutralize MV strain Edmonston. In addition, it was shown that, in sera from naturally immune donors, the majority of VN antibodies are specific for MV H protein, but up to 10 % of neutralizing antibodies are specific for MV F protein.

scholarly journals Comparison of wild-type and subacute sclerosing panencephalitis strains of measles virus. Neurovirulence in ferrets and biological properties in cell cultures.

1978 ◽  
Vol 148 (3) ◽  
pp. 674-691 ◽  
Author(s):  
H Thormar ◽  
P D Mehta ◽  
H R Brown
Keyword(s):  
Cell Fusion ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Biological Properties ◽  
The Other ◽  
Wild Type ◽  
Free Virus ◽  
Other Hand ◽  
The Brain ◽  
Virus Strains

The neurovirulence of two wild type (wt) and seven Subacute Sclerosing Panencephalitis (SSPE) measles virus strains was tested in young adult ferrets by intracerebral (IC) inoculation of infected Vero cell suspensions. Wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S did not produce a detectable encephalitis in the ferrets, but caused a significant formation of serum antibodies against measles virus. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were all neurovirulent in ferrets, particularly strain D.R. which caused an acute encephalitis in all inoculated animals. Strain Biken was of particular interest since it caused a subacute encephalitis in four of seven ferrets. The subacute encephalitis was characterized by a long incubation time, persistence of virus in the brain for at least 8 mo, widespread inflammatory lesions, and production of measles virus specific IgG in the brain. A study of the biological properties of the various measles virus strains showed that wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S produced free virus particles in significant titers both in Vero and ferret brain (FB) cultures. Cytopathic effect (CPE) with cell-fusion was marked in Vero cultures, whereas only minimal CPE and no cell-fusion were observed in the FB cultures. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were mostly cell-associated in Vero and FB cultures, although atypical cell-free particles were produced by strains Biken and IP-3. All four strains showed cell-fusing activity in FB cultures, particularly strain D.R., which was the only strain that spread more actively by fusion in FB than in Vero cultures. The results are discussed in relation to the neurovirulence of the various measles virus strains in adult ferrets. Pronounced cell-fusing activity in FB cells and cell-association with minimal or no production of cell-free virus seem to be essential to establish a brain infection in the animals.

Critical site differences of fusion protein between wildtype and vaccine measles virus strains in Indonesia

2011 ◽  
Vol 51 (3) ◽  
pp. 123
Author(s):  
Made Setiawan ◽  
Agus Sjahrurachman ◽  
Fera Ibrahim ◽  
Agus Suwandono
Keyword(s):  
Protein Binding ◽  
Binding Site ◽  
Measles Virus ◽  
Protein Binding Site ◽  
High Morbidity ◽  
Wild Type ◽  
F Protein ◽  
H Protein ◽  
Type Strains ◽  
Virus Strains

Background Measles virus can cause high morbidity and mortality in infants and children. Fusion glycoprotein (F protein) found in the viral envelope is important for the host cell infection mechanism. F protein is immunogenic and may cause specific immune responses in the host. High variability is found in the F protein gene of vaccine viral strains compared to 'Wild type strains. This amino add sequence variability may result in a less specific immune response against other strains, possibly rendering thevaccine to be less effective.Objective To detennine the amino add sequence differences in critical sites of F protein in Mld type and vaccine measles virus strains in Indonesia.Methods We compared amino acid sequences of three genotypes of Mld type measles virus (02, 03 and D9) to those of the vaccine strains, CAM􀀸 70, Schwarz, and Edmonston􀀸wt type measles virus.Resul ts Analysis showed that there were differences at Fl􀀸F2 cleavage site, B cell epitopes, and H protein binding site between the CAM􀀸70 vaccine viral strains and Mld type strains. Schwarz vaccine strain differed from the wild type strains at the H protein binding site. A 03 wild type strain potential glycosylation site was also different from all other strains studied.Conclusion There were differences in the critical sites of F protein between Mld type strains and the CAM􀀸70 and Schwarz vaccine strains. 

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