A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.

There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Evaluating the impact of human flow on the spread of infectious diseases.

This study explores infectious disease transmission through contact during daily trips between municipalities. We propose an extended susceptible-infectious-recovered model that considers daily movements on the spatial spread of infectious disease. The current model considers two types of movement: long-term movements such as migration and shorter activities completed within a day. We present analytical results using a next-generation matrix and numerical results using actual human flow data, focusing on the number of days it takes for an outbreak from each region to reach the entire area. Our results suggest that the likelihood of infection depends on the ratio of human flow to population rather than the population per se.

PMEL p.Leu18del dilutes coat color of Kumamoto sub-breed of Japanese Brown cattle.

BACKGROUND: Coat color is important for registration and maintenance of livestock. Standard coat color of Kumamoto sub-breed of Japanese Brown cattle is solid brown, but individuals with diluted coat color have been observed recently. In this study, we attempted to identify polymorphism(s) responsible for coat color dilution by whole genome analysis. RESULTS: One of the diluted cattle possessed 7302 exonic polymorphisms which could affect genes' function. Among them, 14 polymorphisms in 10 coat color-related genes were assumed to be specific for the diluted cattle. Subsequent genotyping with three diluted cattle and 74 standard cattle elucidated that PMEL p.Leu18del was the causative polymorphism for coat color dilution in this sub-breed. Individuals with del/del type of this polymorphism showed diluted coat color, but coat color of heterozygotes were intermediate with various dilution rates. CONCLUSIONS: Coat color dilution of Kumamoto sub-breed was caused by PMEL p.Leu18del. The causative del allele has been detected in several genetically distant cattle breeds, suggesting that PMEL p.Leu18del can be used as a DNA marker to control cattle coat color.

Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients.

OBJECTIVE: Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. METHODS: Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. RESULTS: Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/µL and 40 ppb, respectively. CONCLUSIONS: Blood eosinophil and FeNO could predict benralizumab effectiveness.

Evaluation of abdominal aortic calcification by plain CT predicts anastomotic leakage in laparoscopic surgery for colorectal cancer.

BACKGROUND: Anastomotic leakage is one of the most severe and critical complications of laparoscopic surgery for colorectal cancer. However, definitive preoperative predictors of anastomotic leakage remain elusive. With the ageing of society, the number of colorectal cancer patients with arteriosclerotic disease in Japan is increasing. This study was performed to evaluate the correlation between preoperative arteriosclerosis and anastomotic leakage. METHODS: In total, 98 patients undergoing laparoscopic surgery for colorectal cancer with reconstruction using the double-stapling technique without diversion of the stoma were enrolled in the study. Preoperative assessment of arteriosclerotic disease was performed by abdominal computed tomography. The calcification volume percentage of the aorta between the level of the celiac artery root and aortic bifurcation was calculated using ZIOstation2 software, and the relationship between arteriosclerosis and anastomotic leakage was analysed. RESULTS: Among 98 cases, anastomotic leakage was observed in 16 (16.3%). The median calcification volume percentage (range) was 2.35% (0-40.3%). Age, male sex, hypertension, dissection number, estimated glomerular filtration rate and tumour location were correlated with anastomotic leakage on statistical analysis. Statistical analysis showed that calcification volume percentage was one of the robust risk factors for anastomotic leakage (odds ratio: 1.09, 95% confidence interval: 1.03-1.17, P < 0.01). CONCLUSIONS: Calcification of the abdominal aorta may be a promising predictor of AL after laparoscopic surgery for colorectal cancer reconstruction using the double-stapling technique.

Impact of intraoperative hypocapnia on postoperative complications in laparoscopic surgery for colorectal cancer.

PURPOSE: In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO2) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO2 on postoperative complications in LS for CRC. METHODS: In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO2 < 35 mmHg and > 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed. RESULTS: The median (range) durations of hypocapnia and hypercapnia were 2.0 (0-8.3) h and 0.3 (0-5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03-1.36, p = 0.01]. CONCLUSION: Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC.

Early dark cortical band sign on CT for differentiating clear cell renal cell carcinoma from fat poor angiomyolipoma and detecting peritumoral pseudocapsule.

OBJECTIVES: To retrospectively evaluate whether the early dark cortical band (EDCB) on CT can be a predictor to differentiate clear cell renal cell carcinoma (ccRCC) from fat poor angiomyolipoma (Fp-AML) and to detect peritumoral pseudocapsules in ccRCC. METHODS: The EDCBs, which are comprised of unenhanced thin lines at the tumor-renal cortex border in the corticomedullary phase, on the CT images of 342 patients who underwent partial nephrectomy were evaluated. Independent predictors among the clinical and CT findings for differentiating ccRCC from Fp-AML were identified using multivariate analyses. The diagnostic performance of the EDCB for diagnosing peritumoral pseudocapsule in ccRCC and differentiating ccRCC from Fp-AML was calculated. RESULTS: The EDCB was observed in 157 of 254 (61.8%) ccRCCs, 4 of 31 (12.9%) chromophobe RCCs, 1 of 21 (4.8%) papillary RCCs, 3 of 11 (27.3%) clear cell papillary RCCs, 3 of 8 (37.5%) oncocytomas, and 0 of 17 (0%) Fp-AMLs. There was substantial interobserver agreement for the EDCB (k = 0.719). The EDCB was a significant predictor for differentiating ccRCC from Fp-AML (p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of the EDCB for differentiating ccRCC from Fp-AML were 61.8%, 100%, 100%, and 14.9%, respectively, and those for detecting pseudocapsule in 236 ccRCCs were 62.3%, 68.8%, 96.5%, and 11.7%, respectively. CONCLUSION: Although diagnostic accuracy of the EDCB for detecting peritumoral pseudocapsule in RCC is inadequate, it can be a predictor for differentiating ccRCC from Fp-AML with high specificity and PPV. KEY POINTS: • The early dark cortical band (EDCB) sign is observed in nearly two-thirds of clear cell renal cell carcinoma (ccRCC) that are treated by partial nephrectomy and have substantial interobserver agreement. • The EDCB is a significant predictor for differentiating ccRCCs from fat poor angiomyolipomas, with a high specificity and positive predictive value. • Diagnostic accuracy of the EDCB for detecting peritumoral pseudocapsule in ccRCC is inadequate, though better than those in the nephrographic and excretory-phase images.

The effect of men who have sex with men (MSM) on the spread of sexually transmitted infections.

Sexually transmitted infections (STIs) have remained a worldwide public health threat. It is difficult to control the spread of STIs, not only because of heterogeneous sexual transmission between men and women but also because of the complicated effects of sexual transmission among men who have sex with men (MSM) and mother-to-child transmission. Many studies point to the existence of a 'bisexual bridge', where STIs spread from the MSM network via bisexual connections. However, it is unclear how the MSM network affects heterosexual networks as well as mother-to-child transmission. To analyse the effect of MSM on the spread of STIs, we divided the population into four subpopulations: (i) women, (ii) men who have sex with women only (MSW), (iii) men who have sex with both men and women (MSMW), (iv) men who have sex with men exclusively (MSME). We calculated the type-reproduction numbers of these four subpopulations, and our analysis determined what preventive measures may be effective. Our analysis shows the impact of bisexual bridge on the spread of STIs does not outweigh their population size. Since MSM and mother-to-child transmission rates do not have a strong synergistic effect when combined, complementary prevention measures are needed. The methodologies and findings we have provided here will contribute greatly to the future development of public health.

Narrowing of the remnant portal vein diameter and decreased portal vein angle are risk factors for portal vein thrombosis after perihilar cholangiocarcinoma surgery.

PURPOSE: To evaluate the incidence, risk factors, management options, and outcomes of portal vein thrombosis following major hepatectomy for perihilar cholangiocarcinoma. METHODS: A total of 177 perihilar cholangiocarcinoma patients who (1) underwent major hepatectomy and (2) underwent investigating the portal vein morphology, which was measured by rotating the reconstructed three-dimensional images after facilitating bone removal using Aquarius iNtuition workstation between 2002 and 2018, were included. Risk factors were evaluated using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: Six patients developed portal vein thrombosis (3.4%) within a median time of 6.5 (range 0-22) days. Portal vein and hepatic artery resection were performed in 30% and 6% patients, respectively. A significant difference in the probability of the occurrence of portal vein thrombosis (PV) within 30 days was found among patients with portal vein resection, a postoperative portal vein angle < 100°, remnant portal vein diameter < 5.77 mm, main portal vein diameter > 13.4 mm, and blood loss (log-rank test, p = 0.003, p = 0.06, p < 0.0001, p = 0.01, and p = 0.03, respectively). Decreasing the portal vein angle and narrowing of the remnant PV diameter remained significant predictors on multivariate analysis (p = 0.027 and 0.002, respectively). Reoperation with thrombectomy was performed in four patients, and the other two patients were successfully treated with anticoagulants. All six patients subsequently recovered and were discharged between 25 and 70 days postoperatively. CONCLUSION: Narrowing of the remnant portal vein diameter and a decreased portal vein angle after major hepatectomy for perihilar cholangiocarcinoma are significant independent risk factors for postoperative portal vein thrombosis.

Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case-control study of a single center.

BACKGROUND: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. METHODS: To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case-control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. RESULTS: There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). CONCLUSION: This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

Oscillometry as a Predictor of Exercise Tolerance in COPD.

The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) <350 m in the 6-minute walk test (6MWT).This was a prospective, observational study. Fifty-seven subjects with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between April 2015 and April 2016 (54 males; median age, 70 years; and %FEV1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD <350 m, and the predictor of 6MWD <350 m was assessed.Of the 57 total subjects, 43 (75.4%) had a 6MWD ≥350 m, and 14 (24.6%) had a 6MWD <350 m. Between the two groups, there were significant differences in mMRC scale, GOLD stages, CAT scores, FEV1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD <350 m was independently predicted by CAT scores (OR 1.15, 95% CI: 1.01-1.30) and inspiratory R5 (OR 6.01, 95% CI: 1.09-33.30). In receiver operating characteristic curves, the area under the curve was 0.76, 0.78, and 0.85 for CAT scores, R5, and CAT scores + R5, respectively, with the best cutoff value of 17 and 2.82 cmH20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.

Computed tomography imaging characteristics of clear cell papillary renal cell carcinoma.

PURPOSE: Clear cell papillary (CCP) renal cell carcinoma (RCC) is a new subtype of RCC that was formally recognized by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia in 2013. Subsequently, CCP RCC was added to the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. In this study, we retrospectively investigated the computed tomography (CT) findings of pathologically diagnosed CCP RCC. MATERIALS AND METHODS: This study included 12 patients pathologically diagnosed with CCP RCC at our institution between 2015 and 2017. We reviewed the patient's CT data and analyzed the characteristics. RESULTS: Nine solid masses and 3 cystic masses with a mean tumor size of 22.7 ± 9.2mm were included. Solid masses exhibited slight hyper-density on unenhanced CT with a mean value of 34 ± 6 Hounsfi eld units (HU), good enhancement in the corticomedullary phase with a mean of 195 ± 34HU, and washout in the nephrogenic phase with a mean of 133 ± 29HU. The walls of cystic masses enhanced gradually during the corticomedullary and nephrogenic phases. Solid and cystic masses were preoperatively diagnosed as clear cell RCC and cystic RCC, respectively. CONCLUSIONS: The CT imaging characteristics of CCP RCCs could be categorized into either the solid or cystic type. These masses were diagnosed radiologically as clear cell RCC and cystic RCC, respectively.

Diagnosis by 64-Row Multidetector Computed Tomography for Longitudinal Superficial Extension of Distal Cholangiocarcinoma.

BACKGROUND: This study aimed to demonstrate the diagnostic ability of 64-row multidetector computed tomography (64-row MDCT) for longitudinal superficial extension of distal cholangiocarcinoma (LSEDC). METHODS: Twenty-seven patients with distal cholangiocarcinoma (DC) underwent preoperative 64-row MDCT without drainage tubes. LSEDC was diagnosed using curved planar reconstruction images reconstructed from 64-row MDCT, which were compared with pathologic findings. RESULTS: LSEDC was observed in 13 patients (48%). Ten patients (37%) had enhancing nonthickened bile ducts extending continuously from the main tumor (type 1). These coincided with pathologic findings of high-grade dysplasia (HGD) in 90.0% of cases; that is, a positive predictive value (9/10). Fourteen patients (52%) had only wall thickening of the main tumor with or without enhancement (type 2). Four patients with HGD in this group were difficult to diagnose. Three patients (11%) had enhancing nonthickened bile ducts not in continuity with the main tumor (type 3). This finding revealed an inflammatory change instead of a carcinoma in the pathologic findings. The sensitivity and specificity of detecting HGD were 75% and 93% on the liver side, 33% and 100% on the duodenal side, respectively. Four patients (67%) with HGD on the liver side were overdiagnosed, and one patient (17%) was underdiagnosed. Most of the patients overdiagnosed on the liver side (3/4 or 75%) had drainage tubes inserted before the MDCT. CONCLUSIONS: For DC patients without drainage tubes, the 64-row MDCT technique may be useful for diagnosing HGD depicted as LSEDC on the liver side but not as useful on the duodenal side.

A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.

BACKGROUND: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains-the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64-and measured the time-course of experimental data in cell culture. METHODS: We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains. RESULTS AND CONCLUSIONS: We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID50, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.

Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model.

BACKGROUND: Tetherin is an intrinsic anti-viral factor impairing the release of nascent HIV-1 particles from infected cells. Vpu, an HIV-1 accessory protein, antagonizes the anti-viral action of tetherin. Although previous studies using in vitro cell culture systems have revealed the molecular mechanisms of the anti-viral action of tetherin and the antagonizing action of Vpu against tetherin, it still remains unclear how Vpu affects the kinetics of HIV-1 replication in vivo. RESULTS: To quantitatively assess the role of Vpu in viral replication in vivo, we analyzed time courses of experimental data with viral load and target cell levels in the peripheral blood of humanized mice infected with wild-type and vpu-deficient HIV-1. Our recently developed mathematical model describes the acute phase of this infection reasonably, and allowed us to estimate several parameters characterizing HIV-1 infection in mice. Using a technique of Bayesian parameter estimation, we estimate distributions of the basic reproduction number of wild-type and vpu-deficient HIV-1. This reveals that Vpu markedly increases the rate of viral replication in vivo. CONCLUSIONS: Combining experiments with mathematical modeling, we provide an estimate for the contribution of Vpu to viral replication in humanized mice.

Dual adrenal venous phase contrast-enhanced MDCT for visualization of right adrenal veins in patients with primary aldosteronism.

PURPOSE: To evaluate the frequency of visualization of the right adrenal vein (RAV) on dual adrenal venous phase multi-detector computed tomography (MDCT) in patients with primary aldosteronism. MATERIALS AND METHODS: Images of contrast-enhanced dual adrenal venous phase MDCT (45- and 55-second delays) in 90 patients with primary aldosteronism who underwent adrenal venous sampling were retrospectively evaluated. The degree of RAV visualization on each phase image was evaluated by two radiologists using a five-point scale and RAV visualization rates were estimated. RESULTS: The RAV visualization rates on the first- and second-phase images were 89 % and 91 % by radiologist A, and 93 % and 90 % by radiologist B, respectively. No significant differences in the score of RAV visualization were observed between the first- and second-phase images by the two readers (P = 0.164 and P = 0.06). The kappa values for inter-observer agreement of RAV visualization on the first- and second-phase images were 0.57 and 0.46, respectively. The consensual RAV visualization rates on the first- and second-phase images were 91 % and 92 %, respectively. The overall RAV visualization rate by using both phase images was 98 %. CONCLUSION: Dual adrenal venous phase MDCT can visualize the RAV in almost all patients with primary aldosteronism. KEY POINTS: • Dual adrenal venous phase MDCT images can visualize the right adrenal veins. • The adrenal venous phase lies between the arterial and portal phases. • Anatomical information will contribute to the technical success of adrenal venous sampling.

Quantification of deaminase activity-dependent and -independent restriction of HIV-1 replication mediated by APOBEC3F and APOBEC3G through experimental-mathematical investigation.

APOBEC3F and APOBEC3G cytidine deaminases potently inhibit human immunodeficiency virus type 1 (HIV-1) replication by enzymatically inserting G-to-A mutations in viral DNA and/or impairing viral reverse transcription independently of their deaminase activity. Through experimental and mathematical investigation, here we quantitatively demonstrate that 99.3% of the antiviral effect of APOBEC3G is dependent on its deaminase activity, whereas 30.2% of the antiviral effect of APOBEC3F is attributed to deaminase-independent ability. This is the first report quantitatively elucidating how APOBEC3F and APOBEC3G differ in their anti-HIV-1 modes.

A conservation law for virus infection kinetics in vitro.

Conservation laws are among the most important properties of a physical system, but are not commonplace in biology. We derived a conservation law from the basic model for viral infections which consists in a small set of ordinary differential equations. We challenged the conservation law experimentally for the case of a virus infection in a cell culture. We found that the derived, conserved quantity remained almost constant throughout the infection period, implying that the derived conservation law holds in this biological system. We also suggest a potential use for the conservation law in evaluating the accuracy of experimental measurements.