Información del artículo
La mayoría de estudios realizados en cepas gripales aviares parecen indicar que la virulencia es un fenómeno poligénico. Sin embargo, parece demostrado que la hemaglutinina (HA) y la neuraminidasa (NA) y los genes que las codifican (genes 4 y 6) desempeñan un papel esencial en la patogenia viral. Las cepas aviares pueden clasificarse en avirulentas o virulentas en función de la capacidad de la HA para ser activada por endoproteasas sólo del tracto respiratorio o por proteasas de otros tejidos. Esta capacidad se basa en la aparición progresiva de mutaciones que comportan la sustitución de los aminoácidos habituales en el punto de hidrólisis de la HA por otros de tipo básico que determinan la ampliación del espectro de hidrólisis y activación. La NA participa en la adquisición de virulencia a través de su capacidad para unirse al plasminógeno e incrementando la concentración de proteasas activadoras. La adaptación al huésped, a través del reconocimiento del receptor celular, es otro factor que determina la virulencia y la transmisión interespecies de las cepas aviares. Desde el punto de vista epidemiológico sería recomendable, además de la subtipificación de las cepas gripales, determinar la capacidad de activación de la HA para conocer su grado de virulencia.
Most studies performed in avian viral strains seem to indicate that virulence is a polygenic phenomenon. However, hemagglutinin and neuraminidase and the genes codifying these substances (genes 4 and 6) play an essential role in viral pathogenesis. Avian strains can be classified as avirulent or virulent according to the ability of hemagglutinin to be activated by endoproteases of the respiratory tract only or by proteases from other tissues. This ability is based on the progressive development of mutations that lead to the substitution of the normal amino acids at the point of hemagglutinin hydrolysis by the other basic amino acids that determine the amplification of the spectrum of hydrolysis and activation. Neuraminidase participates in the acquisition of virulence through its capacity to bind to plasminogen and by increasing the concentration of activating proteases. Adaptation to the host, through recognition of the cell receptor, is another factor determining the virulence and interspecies transmission of avian strains. From an epidemiological point of view, viral strains should be subtyped and the activating capacity of hemagglutinin should be determined to edentify their degree of virulence.
Palabras clave:
Gripe
Factores de virulencia
Hemaglutinina
Neuraminidasa
El Texto completo está disponible en PDF
Bibliografía
[1.]
F.G. Hayden, P. Palese.
Influenza virus.
Clinical virology, pp. 911-942
[2.]
T. Ito, Y. Kawaoka.
Alivian influenza.
Textbook of influenza, pp. 126-136
[3.]
P.F. Wright, R.G. Webster.
Orthomyxoviruses.
Fields virology, 4.aed, pp. 1533-1579
[4.]
R.A. Lamb, R.M. Krug.
Orthomyxoviridiae: The viruses and their replication.
Fields virology, 4.aed, pp. 1487-1532
[5.]
R.G. Webster, W.J. Bean, O.T. Gorman, T.M. Chambers, Y. Kawaoka.
Evolution and ecology of influenza A viruses.
Microbiol Rev, 56 (1992), pp. 152-179
[6.]
R.G. Webster.
Predictions for future human influenza padermics.
J Infect Dis, 176 (1997), pp. S9-S14
[7.]
Prieto J. Reina, Martínez F. Ballesteros.
La gripe en el siglo XXI: preparándonos para una nueva pandemia.
Rev Clin Esp, 200 (2000), pp. 113-115
[8.]
K.L. Tyler, N. Nathanson.
Pathogenesis of viral infections.
Fields virology, 4.aed, pp. 199-243
[9.]
R.G. Webster, W.J. Bean, O.T. Gorman, T.M. Chambers, Y. Kawaoka.
Evolution and ecology of influenza A viruses.
Microbiol Rev, 56 (1992), pp. 152-179
[10.]
T. Horimoto, Y. Kawaoka.
Pandemic threat posed by avian influenza A viruses.
Clin Microbiol Rev, 14 (2001), pp. 129-149
[11.]
R.G. Webster.
A molecular whodunit.
Science, 293 (2001), pp. 1774-1775
[12.]
M. Hatta, P. Gao, P. Halfmann, Y. Kawaoka.
Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.
Science, 293 (2001), pp. 1840-1842
[13.]
G.K. Hirst.
Agglutination of red cells by allantoid fluid of chick embryos infected with influenza virus.
Science, 94 (1941), pp. 22-23
[14.]
A.G. Porter, C. Barber, N.H. Carey.
Complete nucleotide sequence of an influenza virus hemagglutinin gene from cloned DNA.
Nature, 282 (1979), pp. 471-477
[15.]
D.A. Steinhauer.
Role of hemagglutinin cleavage for the pathogenicity of influenza virus.
Virology, 258 (1975), pp. 1-20
[16.]
H.D. Klenk, R. Rott, M. Orlich, J. Blodorn.
Activation of influenza A viruses by trypsin treatment.
Virology, 68 (1975), pp. 426-439
[17.]
S.G. Lazarowitz, P.W. Choppin.
Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide.
Virology, 68 (1975), pp. 440-454
[18.]
W. Garten, H.D. Klenk.
Understanding influenza virus pathogenicity.
Trends Microbiol, 7 (1999), pp. 99-100
[19.]
D.E. Swayne, D.L. Suarez.
Highly pathogenic avian influenza.
Rev Sci Tech Off Int Epiz, 19 (2000), pp. 463-482
[20.]
M.L. Perdue.
How can a virus suddenly become very pathogenic?.
World Poultry Special Issue, 2000 (2000), pp. 9-10
[21.]
D.E. Swayne, D.L. Suarez.
Evolution and pathobiology of avian influenza virus virulence in domestic birds.
Emergence and control of zoonotic ortho- and paramyxovirus diseases, pp. 35-42
[22.]
K. Tobita, A. Sugiura, C. Enomoto, M. Furuyama.
Plaque assay and primary isolation of influenza A viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin.
Med Microbiol Immunol, 162 (1975), pp. 9-14
[23.]
F.X. Bosch, M. Orlich, H.D. Klenk, R. Rott.
The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses.
Virology, 95 (1979), pp. 197-207
[24.]
F.X. Bosch, W. Garten, H.D. Klenk, R. Rott.
Proteolytic clevage of influenza virus hemagglutinin: Primary structure of the connecting peptide between HA1 and HA2 determines proteolytic clevability and pathogenicity of avian influenza viruses.
Virology, 113 (1981), pp. 725-735
[25.]
I. Günther, B. Glatthaar, G. Döller, W. Garten.
A H1 hemagglutinin of a human influenza A virus with a carbohydrate-modulated receptor binding site and an unusual cleavage site.
Virus Res, 27 (1993), pp. 147-160
[26.]
D.A. Senne, B. Panigraphy, Y. Kawaoka, J.E. Pearson, J. Süss, M. Lipkind, et al.
Survey of the hemagglutinin (HA) cleavage site sequence of H5 and H7 avian influenza viruses: amino acid sequence at the HA cleavage site as a marker of pathogenicity potential.
Avian Dis, 40 (1996), pp. 425-437
[27.]
Y. Kawaoka, R.G. Webster.
Sequence requirement for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells.
Proc Natl Acad Sci (USA, 85 (1988), pp. 324-328
[22.]
J.M. Katz, X. Lu, T.M. Tumpey, C.B. Smith, M.W. Shaw, K. Subbarao.
Molecular correlates of influenza A H5N1 pathogenesis in mice.
J Virol, 74 (2000), pp. 1807-1810
[29.]
Y. Kawaoka, R.G. Webster.
Interlay between carbohydrate in the stalk and the length of the connecting peptide determines the cleavability of influenza virus hemagglutinin.
J Virol, 63 (1989), pp. 3296-3300
[30.]
K.F. Shortridge, M. Peiris, Y. Guan, K. Dyrting, T. Ellis, L. Sims.
H5N1 virus: Beaten, but is it vanquished?.
Emergence and control of zoonotic ortho- and paramyxovirus diseases, pp. 91-97
[31.]
T. Horimoto, Y. Kawaoka.
Reverse genetics provides direct evidence for a correlation of hemagglutinin clevability and virulence of an avian influenza A virus.
J Virol, 68 (1994), pp. 3120-3128
[32.]
W. Garten, H.D. Klenk.
Characterization of the carboxypeptidase involved in the proteolytic cleavage of the influenza hemagglutinin.
Intervirology, 20 (1983), pp. 181-189
[33.]
Y. Kawaoka.
Structural features influencing hemagglutinin cleavability in a human influenza A virus.
J Virol, 65 (1991), pp. 1195-1201
[34.]
R. Ohuchi, M. Ohuchi, W. Garten, H.D. Klenk.
Human influenza virus hemagglutinin with high sensitivity to proteolytic activation.
J Virol, (1991), pp. 3530-3537
[35.]
M.L. Perdue, M. Garcia, J. Beck, M. Brugh, D.E. Swayne.
An Arg-Lys insertion at the hemagglutinin cleavage site of an H5N2 avian influenza isolate.
Virus Genes, 12 (1996), pp. 77-84
[36.]
D.E. Swayne, M.L. Perdue, M. Garcia, E. Rivera-Cruz, M. Brugh.
Pathogenicity and diagnosis of H5N2 mexican avian influenza viruses in chickens.
Avian Dis, 41 (1997), pp. 335-346
[37.]
J.E. Pearson.
Report of the Committee on transmissible diseases of poultry and other avian species. Avian influenza.
Proc 98th Ann Meet US Animal Health Assoc, pp. 519-521
[38.]
D.E. Swayne, J.R. Beck, M. Garcia, M.L. Perdue, M. Brugh.
Pathogenicity shifts in experimental avian influenza virus infections.
Proc 4th Intl Symp Avian Influenza, pp. 171-181
[38.]
H.D. Klenk, W. Garten.
Host cell proteases controlling virus pathogenicity.
Trends Microbiol, 2 (1994), pp. 39-43
[39.]
R. Rott, H.D. Klenk, Y. Nagai, M. Tashiro.
Influenza viruses, cell enzymes and pathogenicity.
Am J Respir Crit Care Med, 152 (1995), pp. S16-S19
[40.]
B. Gotoh, T. Ogasawara, T. Toyoda, N.M. Inocencio, M. Hamaguchi, Y. Nagai.
An endoprotease homologous to the blood clotting factor X as a determinant of viral tropism in chick embryo.
EMBO J, 9 (1990), pp. 4189-4195
[41.]
H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, et al.
Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein.
J Biol Chem, 267 (1992), pp. 13573-13579
[42.]
M. Tashiro, P. Ciborowski, H.D. Klenk, G. Pulverer, R. Rott.
Role of Staphylococcus protease in the development of influenza pneumonia.
Nature (London, 325 (1987), pp. 536-537
[43.]
H. Scheiblauer, M. Reinacher, M. Tashiro, R. Rott.
Interactions between bacteria and influenza A virus in the development of influenza pneumonia.
J Infect Dis, 166 (1992), pp. 783-791
[44.]
J.A. Walker, T. Sakaguchi, Y. Matsuda, T. Yoshida, Y. Kawaoka.
Location and character of the cellular enzyme that cleaves the hemagglutinin of a virulent avian influenza virus.
Virology, 190 (1992), pp. 278-287
[45.]
P.J. Barr.
Mammalian subtilisins: The long-sought dibasic processing endoproteases.
Cell, 66 (1991), pp. 1-3
[46.]
N.G. Seidah, M. Chretien.
Eukariotic protein processing: Endoproteolysis of precursor proteins.
Curr Opin Biotechnol, 8 (1997), pp. 602-607
[47.]
A.M. Stieneke-Grober, M. Vey, H. Angliker, E. Shaw, G. Thomas, C. Roberts, et al.
Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease.
EMBO J, 11 (1992), pp. 2407-2414
[48.]
T. Horimoto, K. Nakayama, S.P. Smeekens, Y. Kawaoka.
Pro-protein-processing endoproteases PC6 and furin both activate hemagglutinin of virulent avian influenza viruses.
J Virol, 68 (1994), pp. 6074-6078
[49.]
A. Gottschalk.
The specific enzyme of influenza virus and Vibrio cholerae.
Biochim Biophys Acta, 23 (1957), pp. 645-646
[50.]
P. Palese, K. Tobita, M. Ueda, R.W. Compans.
Characterization of temperature sensitive influenza mutants defective in neuraminidase.
Virology, 61 (1974), pp. 397-410
[51.]
W.G. Leaver, P.M. Colman, R.G. Webster.
Influenza virus neuraminidase with hemagglutinin activity.
Virology, 137 (1984), pp. 314-323
[52.]
J. Hausmann, E. Kretzschmar, W. Garten, H.D. Klenk.
N1 neuraminidase of influenza virus A/FPV/Rostock/34 has haemadsorbing activity.
J Gen Virol, 76 (1995), pp. 1719-1728
[53.]
D. Kobasa, M.E. Rodgers, K. Wells, Y. Kawaoka.
Neuraminidase hemadsorption activity, conserved in avian influenza A viruses, does not influence viral replication in ducks.
J Virol, 71 (1997), pp. 6706-6713
[54.]
H. Goto, Y. Kawaoka.
A novel mechanism for the acquisition of virulence by a human influenza A virus.
Proc Natl Acad Sci (USA, 95 (1998), pp. 10224-10228
[55.]
S.G. Lazarowitz, A.R. Goldberg, P.W. Choppin.
Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus: host cell activation of serum plaminogen.
Virology, 56 (1973), pp. 172-180
[56.]
T. Saito, T. Horimoto, Y. Kawaoka, D.A. Senne, R.G. Webster.
Emergence of a potentially pathogenic H5N2 influenza virus in chickens.
Virology, 201 (1994), pp. 277-284
[57.]
T. Chillaud.
Risk factors for recent influenza virus disease outbreaks in animals.
Emergence and control of zoonotic ortho- and paramyxovirus diseases, pp. 65-72
[58.]
T. Horimoto, E. Rivera, J. Pearson, D. Senne, S. Krauss, Y. Kawaoka, et al.
Origin and molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in Mexico.
Virology, 213 (1995), pp. 223-230
[59.]
M. Garcia, J.M. Crawford, J.W. Latimer, E. Rivera-Cruz, M.L. Perdue.
Heterogeneity in the hemagglutinin gene and emergence of the highly pathogenic phenotipe among recent H5N2 avian influenza viruses from Mexico.
J Gen Virol, 77 (1996), pp. 1493-1504
[60.]
M. Ohuchi, M. Orlich, R. Ohuchi, B.E.J. Simpson, W. Garten, H.D. Klenk, et al.
Mutations at the cleavage site of the hemagglutinin alter the pathogenicity of influenza virus A/chick/Penn/83 (H5N2.
Virology, 168 (1989), pp. 274-280
[61.]
T. Harimoto, Y. Kawaoka.
Molecular changes in virulent mutants arising from avirulent avian influenza viruses during replication in 14-day-old embryonated eggs.
Virology, 206 (1995), pp. 755-759
[62.]
M.L. Perdue, M. Garcia, D. Senne.
Virulence-associated sequence duplication at the hemagglutinin cleavage site of avian influenza viruses.
Virus Res, 49 (1997), pp. 173-186
[63.]
M. Orlich, H. Gottwald, R. Rott.
Nonhomologous recombination between the hemagglutinin gene and the nucleoprotein gene of an influenza virus.
Virology, 204 (1994), pp. 462-465
[64.]
D. Khatchikian, M. Orlich, R. Rott.
Increased viral pathogenicity after insertion of a 28S ribosomal RNA sequence into the hemagglutinin gene of an influenza virus.
Nature (London, 340 (1989), pp. 156-157
[65.]
B.R. Murphy, V.S. Hinshaw, D.L. Sly, W.T. London, N.T. Hosier, F.T. Wood, et al.
Virulence of avian influenza A viruses for squirrel monkeys.
Infect Immu, 37 (1982), pp. 1119-1126
[66.]
A.S. Beare, R.G. Webster.
Replication of avian influenza viruses in humans.
Arch Virol, 119 (1991), pp. 37-42
[67.]
V.S. Hinshaw, R.G. Webster, B. Turner.
The perpetuation of orthomyxoviruses and paramyxoviruses in canadian waterfowl.
Can J Microbiol, 26 (1980), pp. 622-629
[68.]
V.S. Hinshaw, R.G. Webster, C.W. Neave, B.R. Murphy.
Altered tissue tropism of human avian reasortant influenza viruses.
Virology, 128 (1983), pp. 260-263
[69.]
R.J. Connor, Y. Kawoda, R.G. Webster, J.C. Paulson.
Receptor specificity in human, avian and equine H2 and H3 influenza virus isolates.
Virology, 205 (1994), pp. 17-23
[70.]
Y. Suzuki.
Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains.
Prog Lipid Res, 33 (1994), pp. 429-457
[71.]
A.S. Gambaryan, A.B. Tuzikov, V.E. Piskarev, S.S. Yamnikova, D.K. Lvov, J.S. Robertson, et al.
Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: Non-egg-adapted human H1 and H3 influenza A and influenza B viruses share a common high binding affinity for 6’ -sialyl (N-acetyllactosamine.
Virology, 232 (1997), pp. 345-350
[72.]
M.N. Matrosovich, A.S. Gambaryan, S. Teneberg, V.E. Pisakarev, S.S. Yamnikova, D.K. Lvov, et al.
Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site.
Virology, 233 (1997), pp. 224-234
[73.]
G.N. Rogers, T.J. Pritchett, J.L. Lane, J.C. Paulson.
Differential sensitivity of human, avian and equine influenza A viruses to glycoprotein inhibitor of infection: selection of receptor specific variants.
Virology, 131 (1983), pp. 394-408
[74.]
G.N. Rogers, J.C. Paulson.
Receptor determinants of human and animal influenza virus isolates: Differences in receptor specificity of the H3 hemagglutinin based on species of origin.
Virology, 127 (1983), pp. 361-373
[75.]
J.S. Cruceiro, J.C. Paulson, L.G. Baum.
Influenza virus strains selectively recognize sialoligosaccharides on human respiratory epithelium: The role of the host cell in selection of hemagglutinin receptor specificity.
Virus Res, 29 (1993), pp. 155-165
[76.]
T. Ito, J.S. Cruceiro, S. Kelm, L.G. Baum, S. Krauss, M.R. Castrucci, et al.
Molecular basis for the generation in pigs of influenza A viruses with pandemic potential.
J Gen Virol, 72 (1998), pp. 7367-7373
[77.]
G.N. Rogers, J.C. Paulson, R.S. Daniels, J.J. Skehel, I.A. Wilson, D.C. Wiley.
Single amino acid substitutions in influenza hemagglutinin change receptor binding specificity.
Nature (London, 304 (1983), pp. 76-78
[78.]
C.W. Naeve, V.S. Hinshaw, R.G. Webster.
Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus.
J Virol, 51 (1984), pp. 567-569
[79.]
L.G. Baum, J.C. Paulson.
The N2 neuraminidase of human influenza virus has acquired a substrate specificity complementary to the hemagglutinin receptor specificity.
Virology, 180 (1991), pp. 10-15
[80.]
M.H. Snyder, A.J. Bucker-White, W.T. London, E.L. Tierney, B.R. Murphy.
The avian influenza virus nucleoprotein gene and specific constellation of avian and human virus polymerase genes each specify attenuation of avian/human influenza A/Pintail/79 reassortant viruses from monkeys.
J Virol, 61 (1987), pp. 2857-2863
[81.]
D.L. Suarez, M.L. Perdue, N. Cox, T. Rowe, C. Bender, J. Huang, D.E. Swayne.
Comparisons of highly virulen H5N1 influenza A viruses isolated from humans and chickens from Hong Kong.
J Virol, 72 (1998), pp. 6678-6688
[82.]
P. Gao, S. Watanabe, T. Ito, H. Goto, K. Wells, M. McGregor, et al.
Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong.
J Virol, 73 (1999), pp. 3184-3189
[83.]
X.H. Lu, T.M. Tumpey, T. Morken, S.R. Zaki, N.J. Cox, J.M. Katz.
A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans.
J Virol, 73 (1999), pp. 5903-5911
[84.]
E.K. Subbarao, A. Klimov, J. Katz, H. Regenery, W. Lim, H. Hall, et al.
Characterization of an avian influenza A (H5N1) virus sioladed from a child with a fatal respiratory illness.
Science, 279 (1998), pp. 393-396
Copyright © 2002. Elsevier España, S.L.. Todos los derechos reservados
