Journal of Medical Virology最新文献

Intra-host diversity is an intricate phenomenon related to immune evasion, antiviral resistance, and evolutionary leaps along transmission chains. SARS-CoV-2 intra-host variation has been well-evidenced from respiratory samples. However, data on systemic dissemination and diversification are relatively scarce and come from immunologically impaired patients. Here, the presence and variability of SARS-CoV-2 were assessed among 71 tissue samples obtained from multiple organs including lung, intestine, heart, kidney, and liver from 15 autopsies with positive swabs and no records of immunocompromise. The virus was detected in most organs in the majority of autopsies. All organs presented intra-host single nucleotide variants (iSNVs) with low, moderate, and high abundances. The iSNV abundances observed within different organs indicate that the virus can mutate at one host site and subsequently spread to other parts of the body. In agreement with previous data from respiratory samples, our lung samples presented no more than 10 iSNVs each. But interestingly, when analyzing different organs we were able to detect between 11 and 45 iSNVs per case. Our results indicate that SARS-CoV-2 can replicate, and evolve in a compartmentalized manner, in different body sites, which agrees with the “viral reservoir” theory. We elaborate on how compartmentalized evolution in multiple organs may contribute to SARS-CoV-2 evolving so rapidly despite the virus having a proofreading mechanism.

Acute-on-chronic liver failure (ACLF) is a severe condition characterized by a systemic inflammatory response and associated with high mortality. Currently, there is no reliable prediction model for long-term prognosis in ACLF. This study aimed to develop and validate a prognostic model incorporating inflammation indexes to predict the long-term outcome of patients with hepatitis B virus-related ACLF (HBV-ACLF). A retrospective analysis of clinical data from HBV-ACLF patients (n = 986) treated at the Third Affiliated Hospital of Sun Yat-sen University between January 2014 and December 2018 was conducted. Patients were randomly divided into training (n = 690) and validation (n = 296) cohorts. The Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses were used to identify independent risk factors for long-term mortality. The following variables were identified as independent predictors of long-term mortality: age, cirrhosis, hepatic encephalopathy, total bilirubin (TBIL), international normalized ratio (INR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-platelet ratio (NPR). A novel nomogram was established by assigning weights to each variable. The C-index of the nomogram was 0.777 (95% confidence interval [CI]: 0.752–0.802). In the training set, the area under the curve (AUC) for predicting mortality at 1, 3, and 12 months was 0.841 (95% CI: 0.807–0.875), 0.827 (95% CI: 0.796–0.859), and 0.829 (95% CI: 0.798–0.859), respectively. The nomogram demonstrated superior predictive performance for 12-month survival compared to the model for end-stage liver disease (MELD) score (0.767, 95% CI: 0.730–0.804, p < 0.001) and the clinical overt sepsis in acute liver failure clinical practice Guidelines-ACLF II score (0.807, 95% CI: 0.774–0.840, p = 0.028). Finally, calibration curves and decision curve analysis (DCA) confirmed the clinical utility of the nomogram. The novel inflammation-based scoring system, incorporating MLR and NPR, effectively predicts long-term mortality in HBV-ACLF patients.

“When you can measure what you are speaking about, and express it in numbers, you know something about it.” is a famous quote attributed to Lord Kelvin. This sentiment puts viral load measurements at the center of virology. Viral load, or more precisely, DNA copy number measurements, are also used to follow infections with human herpesviruses, such as Kaposi sarcoma herpesvirus (KSHV) and Epstein–Barr Virus (EBV). EBV and KSHV are associated with human cancers, and determining their DNA copy numbers in the context of cancer prediction and progression on therapy is of fundamental scientific and translational interest. Yet, there is no generally accepted assay for KSHV DNA quantitation, and KSHV viral load is not used in clinical decision-making. Here, we review the history of KSHV DNA detection assays, explore factors that affect sensitivity and specificity, and describe an automated, high-throughput, real-time quantitative polymerase chain reaction (PCR) assay for KSHV and EBV. In conjunction with a digital PCR assay using the same primer/probe combination, we describe how to determine the absolute KSHV genome copy numbers in plasma, peripheral blood mononuclear cells, saliva, and other easily accessible body fluids.

Co-infections with human papillomavirus (HPV) of multiple genotypes mainly occur due to increased sexual activity. To address the prevalence and trend of HPV co-infections in Japan, HPV-type-specific data from Japanese women (n = 8128) aged < 40 years and newly diagnosed with cervical abnormalities at 24 hospitals between 2012 and 2023 were analyzed. These included cervical intraepithelial neoplasia grade 1/2 (CIN1/2, n = 2745), CIN3/adenocarcinoma in situ (AIS) (n = 3953), and invasive cervical cancer (ICC, n = 1430). For women enrolled in this study since 2019, information on sexual behaviors was collected via a self-administered questionnaire. Time-trend analyses by disease category showed significant declines in the prevalence of multiple HPV infections in CIN1/2 (49.1%−38.3%, p_trend = 0.0004), CIN3/AIS (44.7%–31.5%, p_trend = 0.0002), and ICC (26.7%–10.5%, p_trend < 0.0001) during the last decade. When these data were analyzed separately for women aged 20–29 and 30–39 years, similar declining trends were observed in each disease category. Using data from 2111 women for whom information on sexual history was available, the number of sexual partners was strongly associated with increased multiple HPV infections (p < 0.0001). In conclusion, the declining prevalence of HPV co-infections in cervical cancer and its precursors may reflect a decrease in sexual activity among Japanese women of reproductive age.