Infectious diseases

O’Garra and colleagues describe the immune response to infection with Mycobacterium tuberculosis revealed through the use of transcriptomics and the value of blood transcriptional gene signatures for the diagnosis of tuberculosis.

Saphire and colleagues provide new insight into protective antibody-mediated responses to Ebola virus and how these responses could be harnessed for therapeutic intervention and vaccine strategies.

Sok and Burton highlight recent developments in the discovery and application of antibodies able to neutralize diverse isolates of HIV, known as ‘broadly neutralizing antibodies’.

Screaton and colleagues discuss the role of the adaptive immune response against flaviviruses in protection and pathogenesis, with emphasis on cross-reactive T cell and antibody responses.

Malaria remains a disease of global importance, and a fully protective vaccine is elusive. In this Focus Review, Cockburn and Seder describe how insights into the biology of malaria biology may lead to the design of an effective vaccine.

Emerging viral diseases present a huge and increasingly important global threat to public health systems. Graham and Sullivan discuss the challenges presented by emerging viral diseases and discuss how innovations in technology and policy can address this threat.

Diamond, Screaton and colleagues show that certain cross-reactive neutralizing antibodies to dengue virus have therapeutic activity against Zika virus infection in immune-privileged sites in vivo.

Infection with Zika virus has occurred in areas previously exposed to dengue virus, a closely related flavivirus. Screaton and colleagues find that monoclonal antibodies to dengue virus cross-react with Zika virus and enhance infection.

Dengue virus is an important emerging pathogen, but so far there is no vaccine effective for all serotypes. Screaton and colleagues identify a class of broadly reactive human antibodies focused on an epitope that bridges two virion subunits.

Cross-reactivity to dengue virus serotypes can trigger life-threatening inflammation. Culshaw et al. show that germline-encoded components of dengue-virus-specific TCRs influence antigen engagament and suggest that ‘innate-like’ recognition of the virus might underpin harmful cross-reactivity.

Circulating IgG3 increases in chronic HIV infection. Moir and colleagues describe a negative regulatory role of secreted IgG3 in response to chronic HIV infection through its action on nonconventional CD27^– memory B cells.

Macrophages can be an important niche for chronic viral infection. Walker and colleagues demonstrate that macrophages are intrinsically resistant to CTL-mediated killing and can thereby contribute to the maintenance of HIV reservoirs and chronic inflammation.

Evasion of the immune system and global activation of the immune system are hallmarks of human immunodeficiency virus (HIV) infection. Studies reveal that macrophages might be responsible for HIV-associated pathogenesis via resistance to killing and induction of chronic inflammation.

Chronic infection with human immunodeficiency virus impairs B cell antigen receptor signaling via a newly described mechanism of inhibitory signaling mediated by IgG3 and the IgG Fc receptor FcRγIIb (CD32b).

At least five recent papers have shown an unexpected antigenic relationship between Zika and dengue viruses, with potential implications for vaccines and therapeutics.

Moore and colleagues show that Mycobacterium tuberculosis induces miR-33 and miR-33* in macrophages to inhibit integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation, and to support bacterial replication.

Immunity to one serotype of dengue virus can worsen disease following exposure to another serotype, a process called ‘antibody-dependent enhancement’. Grimes and colleagues characterize the function and structural basis of an unusual, potent and broadly neutralizing antibody that lacks such activity.