Although disease develops within 10 years in most persons infected with human immunodeficiency virus type 1 (HIV-1), some remain symptom-free for prolonged periods.^1,2 Most long-term asymptomatic survivors of HIV-1 infection still have evidence of disease progression in the form of declining CD4+ lymphocyte concentrations. However, some rare persons not only are asymptomatic but also maintain stable levels of CD4+ lymphocytes in the normal or near-normal range. Although the definition of nonprogression may vary, approximately 5 percent of seropositive persons have shown no HIV-related disease or declines in CD4+ cell counts despite 10 or more years of documented HIV-1 infection.² Studying persons with long-term nonprogressive infection may help us to understand the mechanisms by which HIV-1 can be controlled.

A viral block on host protein synthesis: As the coronavirus disease 2019 (COVID-19) pandemic continues to cause devastation, scientists race to increase their understanding of the disease-causing severe acute respiratory syndrome coronavirus 2. Once inside host cells, not only does the virus hijack the cells' translational machinery to make viral proteins, but the virulence factor nonstructural protein 1 (Nsp1) also shuts down translation of host messenger RNA. Thoms et al. determined a 2.6-angstrom resolution cryo–electron microscopy structure of a reconstituted complex of Nsp1 bound to the human 40 S ribosomal subunit and showed that Nsp1 blocks the messenger RNA entry tunnel. A structural inventory of native Nsp1-ribosome complexes from human cells confirms this mechanism. Cellular studies show that the translational shutdown almost completely inhibits the innate immune response. The binding pocket on the ribosome may be a target for drugs to treat COVID-19. Science , this issue p. 1249

Vaccine protection against the human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV) in animal models is proving to be a difficult task. The difficulty is due in large part to the persistent, unrelenting nature of HIV and SIV infection once infection is initiated. SIV with a constructed deletion in the auxiliary gene nef replicates poorly in rhesus monkeys and appears to be nonpathogenic in this normally susceptible host. Rhesus monkeys vaccinated with live SIV deleted in nef were completely protected against challenge by intravenous inoculation of live, pathogenic SIV. Deletion of nef or of multiple genetic elements from HIV may provide the means for creating a safe, effective, live attenuated vaccine to protect against acquired immunodeficiency syndrome (AIDS).