Despite its potency in suppressing HIV-1 replication, antiretroviral therapy (ART) cannot eliminate latent viral reservoirs and is associated with several limitations, such as the need for lifelong treatment and the inherent risk of drug resistance. The quest for an HIV-1 cure has progressed from monotherapeutic approaches to the combinations of multimodal strategies, including neutralizing antibodies, precision genome editing, and management of latent reservoirs. Antibody-based interventions primarily involve inducing broadly neutralizing antibodies (bNAbs) through native-like envelope (Env) trimer vaccines, with their efficacy further enhanced by mRNA-lipid nanoparticle delivery systems. Precision genome editing can be achieved by using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) along with long-acting slow-effective release antiretroviral therapy. Reservoir-targeted therapies are typically implemented by reactivating latent viruses using the “shock and kill” strategy. Engineered cellular therapies include chimeric antigen receptor T (CAR-T) cells or bispecific antibodies (bsAbs) for subsequent immune clearance, immune system reconstitution via stem cell transplantation, and reversal of T-cell exhaustion using immune checkpoint inhibitors. Despite these advances, challenges remain, including suboptimal immunogenicity of Env vaccines, off-target effects and inefficient delivery of gene editing tools, incomplete reactivation of latent viruses, and limitations of preclinical models. Future research should focus on optimizing synergistic effects by improving Env trimer design, enhancing the targeting specificity of CRISPR systems, and developing preclinical models that more accurately reflect human immunity, thereby facilitating the transition from lifelong ART to a functional cure. This review summarizes recent progress in multimodal synergistic strategies and proposes a framework for an HIV-1 cure that may also offer insights into the treatment of other chronic viral infections.

Hand, foot, and mouth disease (HFMD) is one of the most common class C infectious diseases, posing a serious threat to public health worldwide. Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) have been regarded as the major pathogenic agents of HFMD; however, since an outbreak caused by coxsackievirus A6 (CV-A6) in France in 2008, CV-A6 has gradually become the predominant pathogen in many regions. CV-A6 infects not only children but also adults, and causes atypical clinical symptoms such as a more generalized rash, eczema herpeticum, high fever, and onychomadesis, which are different from the symptoms associated with EVA71 and CV-A16. Importantly, the rate of genetic recombination of CV-A6 is high, which can lead to changes in virulence and the rapid evolution of other characteristics, thus posing a serious threat to public health. To date, no specific vaccines or therapeutics have been approved for CV-A6 prevention or treatment, hence it is essential to fully understand the relationship between recombination and evolution of this virus. Here, we systematically review the genetic recombination events of CV-A6 that have occurred worldwide and explore how these events have promoted virus evolution, thus providing important information regarding future HFMD surveillance and prevention.

Human infection with Chlamydia psittaci is rare but difficult to recognize. We report an outbreak of psittacosis among poultry processing workers in China. We applied metagenomic next-generation sequencing and identified Chlamydia psittaci reads from samples of all seven patients, four of which were subsequently confirmed by PCR. Epidemiological results suggested that the poultry processed in the factory was the possible source of human infection.