Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread

Hangartner et al., Journal of Experimental Medicine, 2006, 203: 2033-2042.

Speaker：林雅葶                           Date：2006/10/25, 15:10~16:00

Commentator：陳舜華 老師                  Place：Room 601

Abstract:

Lymphocytic choriomeningitis virus (LCMV) neutralizing antibodies only become detectable at late time point after infection. In contrast, nonneutralizing antibodies, which exhibit specificity for various LCMV proteins, are induced early after infection¹. Nonneutralizing antiviral antibodies can be divided into those that bind to the intact virion surface and “debris-specific” antibodies. Antibodies of the first group either recognize epitopes on the intact virion surface different from those of neutralizing antibodies, or bind the same antigenic site as neutralizing antibodies, but have low affinity/avidity and therefore fail to neutralize the virus². The second group of nonneutralizing antibodies binds to other antigenic moieties and comprises the majority of nonneutralizing antibodies. To examine the possible biological role of the early, low affinity antibodies against LCMV, the authors infected CTL-deficient TgH(KL25) mice with LCMV-WE and isolated virus escape variants at various time points thereafter. Some of the escape variants that arose early after infection could still bind to the KL25 neutralizing antibody. In contrast, no antibody binding could be detected for late isolates. The results indicate that binding, but nonneutralizing, antibodies can exert a selective pressure on the virus. Indeed, infection of naive KL25 mice with the early virus isolates exhibiting antibody binding activity resulted in enhanced virus clearance in a partially complement-dependent manner. It was concluded that nonneutralizing antibodies bound to the same neutralizing antigenic site on the LCMV surfaceglycoprotein can exert an important biological function by limiting early virus spread.

References:

1.          Hangartner et al., Antiviral antibody responses: the two extremes of a wide spectrum. Nat Rev Immunol, 2006, 6: 231-243.

2.          Parekh et al., Proteins of lymphocytic choriomeningitis virus: antigenic topography of the viral glycoproteins. Virology, 1986, 153: 168–178.