2026年 · 第06卷第03期

Background: Zika virus (ZIKV) has been associated with neonatal microcephaly or atypical Guillain-Barré syndrome in adults since 2016. However, despite considerable progress in understanding the biology and pathogenesis of ZIKV infection, little is known about its entry factors. This study aimed to identify host-cell proteins essential for ZIKV entry enriched by labeled viral envelope particles. The identification of solute carrier family 3 member 2 (SLC3A2) (CD98 heavy chain) through this approach highlights its potential as a novel target for therapeutic intervention against ZIKV. Methods: Gene editing via CRISPR-Cas9 and classical virological experiments were performed to identify SLC3A2 functions in ZIKV entry and infection processes. Immunofluorescence, reverse transcription-quantitative polymerase chain reaction, and western blotting technologies were further used to detect viral proteins and genomes. Besides, coimmunoprecipitation and protein/antibody blocking assay were also conducted to identify direct interactions between SLC3A2 and the ZIKV envelope protein. Results: Several human membrane proteins were overexpressed in HEK293 T cells, but only SLC3A2 could significantly promote ZIKV entry into host cells by two- to three- fold compared with the control. During authentic ZIKV infection, the genetic ablation of SLC3A2 in SLC3A2-KO1 JEG-3 cells reduced the viral infection rate to 59.00% ± 5.10% of the wild-type level (100.00% ± 4.97%) (P < 0.001), but its overexpression increased the susceptibility of human placenta- and brain-derived cell lines to the virus. SLC3A2 overexpression increased attached ZIKV levels to 3.4-fold of the control (3.423 ± 0.715 vs. 1.000 ± 0.897, P < 0.001) and internalized ZIKV levels to 1.7-fold of the control (3.782 ± 0.512 vs. 2.293 ± 0.272, P = 0.013) due to direct interaction with the ZIKV envelope protein in U-251MG cells. Our data further showed the close association of SLC3A2 with the ZIKV envelope protein via its extracellular domain during authentic viral infection. Notably, SLC3A2 ectodomain decoys and blocking antibodies markedly reduced ZIKV infection rather than affecting influenza A virus infection. Conclusion: SLC3A2 promotes ZIKV infection in placenta- or brain-derived cells by directly interacting with the ZIKV envelope protein and improving virus entry. SLC3A2 may be implicated in early-phase ZIKV infection as its entry factor, thereby identifying a potential therapeutic target and a basis for formulating antiviral strategies against ZIKV.

Background: The WHO and international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for all treatment-naive (TN) people living with human immunodeficiency virus (HIV) (PLWH). However, data on temporal trends and clinical outcomes of ART initiation and regimen selection among TN PLWH remain limited in China. This study is designed to evaluate the real-world effectiveness of contemporary treatment strategies within the Chinese context. Methods: We conducted a retrospective study of 1,460 TN PLWH who initiated ART between January 2021 and December 2023 at Beijing Ditan Hospital. Data on sex, age, initiation time, ART regimens, CD4 counts, and HIV viral load were collected. Initiation time was categorized based on the time from diagnosis to ART initiation: same-day initiation (0 days), rapid initiation (1 - 7 days), regular initiation (8 - 30 days), and delayed initiation (> 30 days). The main endpoint was the rate of PLWH with virological suppression (HIV-1 RNA < 40 copies/mL) during the study period. Additionally, the durability of ART regimens and the CD4 T-cell count recovery were also evaluated. Factors associated with regimen durability were assessed using univariate and multivariate Cox proportional hazards models. Generalized estimating equations (GEE) were used to identify factors associated with virological suppression among TN PLWH. Results: From 2021 to 2023, the proportion of patients with same-day initiation and that of patients with rapid initiation significantly increased, rising from 8.4% (55/656) to 14.0% (69/493) and from 49.5% (325/656) to 57.6% (284/493), respectively (P < 0.001). Furthermore, 32.9% (46/140) and 36.3% (269/741) of PLWH who underwent same-day and rapid initiation, respectively, chose initial regimens containing two nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor. A representative regimen was efavirenz, lamivudine, and tenofovir disoproxil fumarate (EFV+3TC+TDF). All patients achieved a viral suppression rate of over 95.0% at the 24- and 36-month follow-up visits. In TN PLWH who adhered to initial regimens, GEE analysis of virological suppression factors showed both bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir/lamivudine (DTG/3TC) were non-inferior to EFV+3TC+TDF (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 0.75 - 2.39, P = 0.318; OR = 1.92, 95% CI: 0.54 - 6.80, P = 0.311, respectively). Moreover, BIC/FTC/TAF and DTG/3TC were associated with a lower likelihood of regimen switching, with hazard ratios of 0.35 (P < 0.001) and 0.39 (P = 0.004). Besides, BIC/FTC/TAF achieved CD4 T cell counts above 350 cells/μL significantly earlier (P = 0.015). Conclusion: Our findings revealed the positive trend in rapid initiation in China and several challenges in clinical practice. More targeted interventions are needed to promote the use of BIC/FTC/TAF and DTG/3TC, enhance the accessibility, and ultimately improve health outcomes for PLWH.

Background: An increased incidence of group A Streptococcus-related scarlet fever has been observed in Shanghai since 2011, characterized by the co-circulation of both emm12 and emm1 strains. The comparative virulence potential of these two dominant strains, which is critical for understanding their dynamics and severity, remains largely under researched. This study aimed to systematically compare their virulence determinants to uncover the molecular basis for their successful dissemination. Methods: As the dominant strains that cause scarlet fever, 16 isolates each of both emm1 and emm12 were selected from the Children’s Hospital at Fudan University between 2011 and 2022 using a stratified random sampling method. We compared the two strain types in terms of the positivity rate of virulence factors, adherence and internalization capacity into epithelial cells, biofilm formation capacity, and resistance to innate immune responses. Results: Genomic analysis revealed significant divergence between the emm1 and emm12 strains, particularly within the fibronectin-collagen-T antigen (FCT) region and fibronectin-binding protein and superantigen genes. These genetic differences were reflected in functionally distinct phenotypes. Emm1 strains (linked to FCT2) exhibited a superior colonization capacity, demonstrating rates of epithelial cell adherence and internalization that were approximately two-folds higher, and significantly enhanced biofilm formation compared to emm12 strains (linked to FCT4; P < 0.05). Furthermore, emm1 strains showed significantly greater resistance to innate immune clearance, with higher survival rates in human whole blood, serum, and phagocytic cells (P < 0.001). Conclusions: The enhanced in vitro colonization and immune evasion fitness of emm1 strains are likely attributable to their distinct virulence gene repertoire and expression profile. These findings suggest that the co-dominance of emm1 and emm12 may be driven by divergent pathogenic strategies. The continuous investigation of shifts in the prevalence of emm types and associated virulence factors is essential for understanding their epidemiology and informing strategies for controlling scarlet fever.

The human immunodeficiency virus (HIV) epidemic poses a significant threat to global human health annually. Although antiretroviral therapy can control HIV viremia and delay disease progression, it cannot eliminate the viral reservoir. People living with HIV must rely on antiretroviral medication for their entire lifetime. HIV establishes a persistent viral latent reservoir, which remains an enormous challenge in eradicating HIV infection. With advancements in HIV research, many strategies have emerged to target cells harboring latent HIV. A functional cure for HIV has been proposed as a promising and pragmatic strategic objective. In this review, we provide an overview of current strategies and the latest research progress in the field of HIV cure development, highlighting the opportunities and challenges associated with finding a functional cure for HIV.

Orthohantavirus infections constitute a significant global public health challenge, predominantly presenting as two distinct clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia and hantavirus pulmonary syndrome (HPS) in the Americas. Epidemiological data indicate considerable geographic variability in disease incidence, influenced by intricate interactions among ecological, socioeconomic, and public health determinants. In Asia, a notable reduction in cases has been achieved through enhanced economic conditions, strategic public health initiatives, and effective management of rodent populations. Conversely, Nordic countries continue to report high HFRS incidence, which is attributed to ecological conditions conducive to sustaining reservoir rodent populations. South America has experienced an upward trend in cases, raising concerns about potential large-scale outbreaks, while emerging reports from Africa suggest a possible expansion of endemic regions. Notably, Australia remains one of the few regions without documented orthohantavirus infections and presents a unique epidemiological profile. This review comprehensively examines the global distribution of orthohantavirus infections, analyzes key epidemiological trends, and discusses the environmental and socioeconomic determinants influencing disease dynamics, providing critical insights for public health preparedness and intervention strategies.

Opportunistic infections (OIs) remain a major cause of morbidity and mortality among immunocompromised individuals, and delayed or inaccurate diagnosis can rapidly lead to adverse clinical outcomes. This narrative review critically evaluates the diagnostic performance, clinical utility, and evolving applications of quantitative real-time polymerase chain reaction (qPCR) for detecting opportunistic pathogens in vulnerable patient populations. Evidence across bacterial, fungal, viral, and parasitic infections demonstrates that qPCR consistently surpasses conventional culture- and serology-based methods in sensitivity, specificity, and turnaround time, particularly in cases of low pathogen burden or prior antimicrobial exposure. Its quantitative capability enables dynamic pathogen load monitoring and facilitates timely, targeted therapeutic interventions. However, limitations such as assay variability, incomplete standardization, and challenges in distinguishing colonization from active infection in polymicrobial contexts persist. Ongoing advances in multiplex technologies, digital PCR, and integrative data-driven diagnostics are expected to further refine clinical implementation. Collectively, qPCR has evolved from a supplemental assay to a cornerstone technology in precision diagnostics for OIs in immunocompromised patients.

Evidence regarding infants with chronic hepatitis B virus (HBV) infection receiving antiviral therapy remains limited. In this case series, we describe four infants aged 7-10 months diagnosed with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). CHB01, CHB03, and CHB04 demonstrated active HBV replication and elevated alanine aminotransferase (ALT) levels. CHB02 presented with a relatively low HBV DNA level (3.52 log10 IU/mL), a low hepatitis B surface antigen (HBsAg) titer (4 IU/mL), and a normal ALT level. With parental informed consent, all four infants received lamivudine (LAM) monotherapy before one year of age. Ultimately, all achieved undetectable HBV DNA after a mean of 5.5 months, HBeAg seroconversion at 8.5 months, HBsAg loss at 7.0 months, and functional cure at 11 months on average. This suggests that early initiation of antiviral treatment may help achieve functional cure for infants with HBeAg-positive CHB.

Although hepatitis C virus (HCV) infection is typically diagnosed by anti-HCV antibody testing, rare cases of seronegative HCV infection, defined by detectable HCV ribonucleic acid (RNA) in the absence of antibodies, have been reported in a small number of human immunodeficiency virus (HIV)-positive patients. We describe the case of an HIV-positive patient with persistently elevated alanine aminotransferase levels who was found to have a high HCV RNA viral load (1,140,000 IU/mL) despite a negative HCV antibody screening. The patient had been receiving combination antiretroviral therapy (cART) initially with efavirenz, TAF and 3TC, and was later switched to bictegravir/TAF/3TC. Following hepatological evaluation and initiation of sofosbuvir/velpatasvir therapy, plasma HCV RNA became undetectable. Remarkably, this patient, who maintained a stable immunological profile, also exhibited spontaneous HIV seroreversion, characterized by the loss of detectable HIV-specific antibodies. These observations illustrate the importance of a molecular-based diagnostic approach to complement serological testing in individuals at risk for HIV-related infections.