C1q enables influenza hemagglutinin stem binding antibodies to block viral attachment and broadens the antibody escape repertoire.

Antigenic drift, the gradual accumulation of amino acid substitutions in the influenza virus hemagglutinin (HA) receptor protein, enables viral immune evasion. Antibodies (Abs) specific for the drift-resistant HA stem region are a promising universal influenza vaccine target. Although anti-stem Abs are not believed to block viral attachment, here we show that complement component 1q (C1q), a 460-kilodalton protein with six Ab Fc-binding domains, confers attachment inhibition to anti-stem Abs and enhances their fusion and neuraminidase inhibition. As a result, virus neutralization activity in vitro is boosted up to 30-fold, and in vivo protection from influenza PR8 infection in mice is enhanced. These effects reflect increased steric hindrance and not increased Ab avidity. C1q greatly expands the anti-stem Ab viral escape repertoire to include residues throughout the HA, some of which cause antigenic alterations in the globular region or modulate HA receptor avidity. We also show that C1q enhances the neutralization activity of non-receptor binding domain anti-SARS-CoV-2 spike Abs, an effect dependent on spike density on the virion surface. These findings demonstrate that C1q can greatly expand Ab function and thereby contribute to viral evolution and immune escape.

Reverse Genetics of Dengue Virus.

Dengue virus (DENV) is one of the most important and widespread arthropod-borne viruses, causing millions of infections over the years. Considering its epidemiological importance, efforts have been directed towards understanding various aspects of DENV biology, which have been facilitated by the development of different molecular strategies for engineering viral genomes, such as reverse genetics approaches. Reverse genetic systems are a powerful tool for investigating virus-host interaction, for vaccine development, and for high-throughput screening of antiviral compounds. However, stable manipulation of DENV genomes is a major molecular challenge, especially when using conventional cloning systems. To circumvent this issue, we describe a simple and efficient yeast-based reverse genetics system to recover infectious DENV clones.