Merkel cell polyomavirus large T antigen binding to pRb promotes skin hyperplasia and tumor development.

Clear evidence supports a causal link between Merkel cell polyomavirus (MCPyV) and the highly aggressive human skin cancer called Merkel cell carcinoma (MCC). Integration of viral DNA into the human genome facilitates continued expression of the MCPyV small tumor (ST) and large tumor (LT) antigens in virus-positive MCCs. In MCC tumors, MCPyV LT is truncated in a manner that renders the virus unable to replicate yet preserves the LXCXE motif that facilitates its binding to and inactivation of the retinoblastoma tumor suppressor protein (pRb). We previously developed a MCPyV transgenic mouse model in which MCC tumor-derived ST and truncated LT expression were targeted to the stratified epithelium of the skin, causing epithelial hyperplasia, increased proliferation, and spontaneous tumorigenesis. We sought to determine if any of these phenotypes required the association between the truncated MCPyV LT and pRb. Mice were generated in which K14-driven MCPyV ST/LT were expressed in the context of a homozygous RbΔLXCXE knock-in allele that attenuates LT-pRb interactions through LT's LXCXE motif. We found that many of the phenotypes including tumorigenesis that develop in the K14-driven MCPyV transgenic mice were dependent upon LT's LXCXE-dependent interaction with pRb. These findings highlight the importance of the MCPyV LT-pRb interaction in an in vivo model for MCPyV-induced tumorigenesis.

Effects of Omeprazole on Recurrent Clostridioides difficile Infection Caused by ST81 Strains and Their Potential Mechanisms.

Clostridioides difficile infection (CDI) is associated with high recurrence rates that have substantial effects on patients' quality of life. To investigate the risk factors and potential mechanisms contributing to recurrent CDI (rCDI), a total of 243 cases were enrolled in this study. The history of omeprazole (OME) medication and ST81 strain infection were considered the two independent risks with the highest odds ratios in rCDI. In the presence of OME, we detected concentration-dependent increases in the MIC values of fluoroquinolone antibiotics against ST81 strains. Mechanically, OME facilitated ST81 strain sporulation and spore germination by blocking the pathway of purine metabolism and also promoted an increase in cell motility and toxin production by turning the flagellar switch to the ON state. In conclusion, OME affects several biological processes during C difficile growth, which have fundamental impacts on the development of rCDI caused by ST81 strains. Programmed OME administration and stringent surveillance of the emerging ST81 genotype are matters of considerable urgency and significance in rCDI prevention.

Ultrasonic Phased Array Imaging Approach Using Omni-Directional Velocity Correction for Quantitative Evaluation of Delamination in Composite Structure.

The ultrasonic detectability of buried defects within composite materials is dependent on the anisotropy of the composite material by which the propagation property of acoustic wave in each direction is variably affected. In this study, the characteristics of acoustic waves propagating in different directions for composite materials are explored based on the full matrix capture (FMC) data using an ultrasonic phased array. The elastic constant of multidirectional carbon fiber reinforced plastic (CFRP) laminate is first derived based on the genetic algorithm. The characteristics of transmitted and reflected waves in higher angles are predicted by implementing the Christoffel equation, and the focal law used in post-processing of FMC data can be optimized accordingly. The imaging results of the total focusing method (TFM) using the improved focal law are compared with the results of the conventional TFM. The results suggest that the optimized TFM can effectively characterize the defect by reducing the background noise. Furthermore, since it is impractical to theoretically correct angle-dependent velocity for in situ inspection, a linear extrapolation method based on the experimentally measurable velocity at low angles is proposed to estimate the velocity profile at higher angles. The imaging results using the fast extrapolated velocity profile is then compared with the theoretical, and it has been demonstrated that while the difference between the images using the theoretical focal law and the linearly extrapolated one is barely visible, the later one is overwhelmingly advantageous to be realiszd for engineering practices.

Effects of walking and sun exposure on bone density and balance in elderly with osteopenia.

INTRODUCTION: Bone mineral density (BMD) decreases with age, leading to fractures, decreased mobility, and impaired quality of life. We aimed to determine the effects of brisk walking and exposure to sunlight on BMD and balance in the elderly with osteopenia. MATERIALS AND METHODS: We recruited 81 elderly subjects with osteopenia from January 2019 to March 2019. They were divided into four groups: a daytime-walking group (n = 20), a night-time-walking group (n = 20), a sun-exposure-only group (n = 20), and a control group (n = 21). The subjects walked briskly for 30-60 min three times a week for 24 weeks. The sun-exposure-only group received sunlight for 20-30 min three times a week. All four groups received supplemental calcium. Lumbar L1-L4 BMD, serum 25-hydroxyvitamin D3, timed-up-go-test (TUGT), five-times-sit-stand-test (FTSST), open-eye and closed-eye one-leg-stance-test (OLST) were measured at baseline and 1 day after program completion. RESULTS: The lumbar L1-L4 BMD was higher in all intervention groups (P < 0.05), with the daytime-walking group outperforming the others. There was no significant difference between the night-time-walking and sun-exposure-only groups (P > 0.05). The levels of serum 25-hydroxyvitamin D3 in the daytime-walking and sun-exposure-only groups were higher than those in the night-time-walking and control groups (P < 0.05). The TUGT and FTSST times decreased in all three intervention groups and predominantly so in the daytime-walking group, whereas the open-eye and closed-eye OLST times increased (P < 0.05). CONCLUSION: Brisk walking and sun exposure increase BMD and improve dynamic and static balance in the elderly with osteopenia.

Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.

Merkel cell polyomavirus (MCV) contributes to approximately 80% of all Merkel cell carcinomas (MCCs), a highly aggressive neuroendocrine carcinoma of the skin. MCV-positive MCC expresses small T antigen (ST) and a truncated form of large T antigen (LT) and usually contains wild-type p53 (TP53) and RB (RB1). In contrast, virus-negative MCC contains inactivating mutations in TP53 and RB1. While the MCV-truncated LT can bind and inhibit RB, it does not bind p53. We report here that MCV LT binds to RB, leading to increased levels of ARF, an inhibitor of MDM2, and activation of p53. However, coexpression of ST reduced p53 activation. MCV ST recruits the MYC homologue MYCL (L-Myc) to the EP400 chromatin remodeler complex and transactivates specific target genes. We observed that depletion of EP400 in MCV-positive MCC cell lines led to increased p53 target gene expression. We suspected that the MCV ST-MYCL-EP400 complex could functionally inactivate p53, but the underlying mechanism was not known. Integrated ChIP and RNA-sequencing analysis following EP400 depletion identified MDM2 as well as CK1α, an activator of MDM4, as target genes of the ST-MYCL-EP400 complex. In addition, MCV-positive MCC cells expressed high levels of MDM4. Combining MDM2 inhibitors with lenalidomide targeting CK1α or an MDM4 inhibitor caused synergistic activation of p53, leading to an apoptotic response in MCV-positive MCC cells and MCC-derived xenografts in mice. These results support dual targeting of MDM2 and MDM4 in virus-positive MCC and other p53 wild-type tumors.

Distribution and Antifungal Susceptibility of Candida Species Causing Candidemia in China: An Update From the CHIF-NET Study.

BACKGROUND: Candidemia is the most common, serious fungal infection and Candida antifungal resistance is a challenge. We report recent surveillance of candidemia in China. METHODS: The study encompassed 77 Chinese hospitals over 3 years. Identification of Candida species was by mass spectrometry and DNA sequencing. Antifungal susceptibility was determined using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: In total, 4010 isolates were collected from candidemia patients. Although C. albicans was the most common species, non-albicans Candida species accounted for over two-thirds of isolates, predominated C. parapsilosis complex (27.1%), C. tropicalis (18.7%), and C. glabrata complex (12.0%). Most C. albicans and C. parapsilosis complex isolates were susceptible to all antifungal agents (resistance rate <5%). However, there was a decrease in voriconazole susceptibility to C. glabrata sensu stricto over the 3 years and fluconazole resistance rate in C. tropicalis tripled. Amongst less common Candida species, over one-third of C. pelliculosa isolates were coresistant to fluconazole and 5-flucytocine, and >56% of C. haemulonii isolates were multidrug resistance. CONCLUSIONS: Non-albicans Candida species are the predominant cause of candidemia in China. Azole resistance is notable amongst C. tropicalis and C. glabrata. Coresistance and multidrug resistance has emerged in less common Candida species.

Identification of the role of toxin B in the virulence of Clostridioides difficile based on integrated bioinformatics analyses.

PURPOSE: Clostridioides difficile toxin B (TcdB) plays a critical role in C. difficile infection (CDI), a common and costly healthcare-associated disease. The aim of the current study was to explore the intracellular and potent systemic effects of TcdB on human colon epithelial cells utilizing Gene Expression Omnibus and bioinformatic methods. METHODS: Two datasets (GSE63880 and GSE29008) were collected to extract data components of mRNA of TcdB-treated human colon epithelial cells; "limma" package of "R" software was used to screen the differential genes, and "pheatmap" package was applied to construct heat maps for the differential genes; Metascape website was utilized for protein-protein interaction network and Molecular Complex Detection analysis, and Genome Ontology (GO) was used to analyze the selected differential genes. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to validate the expression of hub genes. RESULTS: GO terms involved in DNA replication and cell cycle were identified significantly enriched in TcdB-treated human colon epithelial cells. Moreover, the decreased expression of DNA replication-related genes, MCM complex, and CDC45 in C. difficile (TcdA-/TcdB+)-infected Caco-2 cells were validated via qRT-PCR and Western blot assays. CONCLUSIONS: In conclusion, the integrated analysis of different gene expression datasets allowed us to identify a set of genes and GO terms underlying the mechanisms of CDI induced by TcdB. It would aid in understanding of the molecular mechanisms underlying TcdB-exposed colon epithelial cells and provide the basis for developing diagnosis biomarkers, treatment, and prevention strategies.

Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.

Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A) subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq) and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.

In Vitro Activities of Ceftaroline/Avibactam, Ceftazidime/Avibactam, and Other Comparators Against Pathogens From Various Complicated Infections in China.

Background: We conducted a national antimicrobial surveillance study of both gram-positive and gram-negative organisms isolated from hospitalized patients. This report presents data on antimicrobial susceptibility among 4998 organisms collected in China between 2012 and 2014. Method: The minimum inhibitory concentrations (MICs) and susceptibilities of ceftaroline/avibactam (CPA), ceftazidime/avibactam (CZA) and a range of comparative agents were determined according to guidelines established by the Clinical and Laboratory Standards Institute (CLSI). Results: The highest overall susceptibility levels for all Enterobacteriaceae during the study period were observed for CPA, CZA, doripenem (DOR), meropenem (MEM), and amikacin (AMK), which were all >90%. However, both CPT and CAZ alone and in combination with avibactam showed low activities for Acinetobacter spp., whereas CPA and CZA exhibited MIC90 values for Pseudomonas aeruginosa that were reduced by 4- and 8-fold, respectively, compared with those of CPT and CAZ. High susceptibilities of Acinetobacter spp. and P. aeruginosa to colistin and P. aeruginosa to AMK were observed. For the gram-positive strains, no significant activity changes were seen for Enterococcus, Staphylococcus, and viridans group streptococci to CPT or CAZ alone or in combination with avibactam, whereas Streptococcus pneumoniae and ß-hemolytic Streptococcus showed almost 100% susceptibility to both CPT and CPA. Conclusion: The addition of 4 mg/L avibactam greatly increased the activities of CPT and CAZ against most Enterobacteriaceae and P. aeruginosa isolates, whereas no significant changes were observed in Acinetobacter spp. or any of the gram-positive strains.

Five-Year National Surveillance of Invasive Candidiasis: Species Distribution and Azole Susceptibility from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study.

Data on the epidemiology of invasive candidiasis (IC) and the antifungal susceptibility of Candida isolates in China are still limited. Here we report on surveillance for IC from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study. Sixty-five tertiary hospitals collected 8,829 Candida isolates from 1 August 2009 to 31 July 2014. Matrix-assisted laser desorption ionization-time of flight mass spectrometry supplemented by ribosomal DNA sequencing was used to define the species, and the fluconazole and voriconazole susceptibilities were determined by the Clinical and Laboratory Standards Institute disk diffusion method. A total of 32 Candida species were identified. Candida albicans was the most common species (44.9%), followed by the C. parapsilosis complex (20.0%), C. tropicalis (17.2%), and the C. glabrata complex (10.8%), with other species comprising <3% of isolates. However, in candidemia, the proportion of cases caused by C. albicans was only 32.3%. C. albicans and C. parapsilosis complex isolates were susceptible to fluconazole and voriconazole (<6% resistance), while fluconazole and azole cross-resistance rates were high in C. tropicalis (13.3% and 12.9%, respectively), C. glabrata complex (18.7% and 14%, respectively), and uncommon Candida species (44.1% and 10.3%, respectively) isolates. Moreover, from years 1 to 5 of the study, there was a significant increase in the rates of resistance to fluconazole among C. glabrata complex isolates (12.2% to 24.0%) and to both fluconazole (5.7% to 21.0%) and voriconazole (5.7% to 21.4%) among C. tropicalis isolates (P < 0.01 for all comparisons). Geographic variations in the causative species and susceptibilities were noted. Our findings indicate that antifungal resistance has become noteworthy in China, and enhanced surveillance is warranted.

Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation.

Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1). Extracellular flux analysis revealed increased lactate export reflecting elevated aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90 cells. Both NF-κB and MYC have been shown to regulate MCT1 expression. While MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased following knockdown of the NF-κB subunit RelA, supporting a synergistic activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more effective than MYC or MYCN in increasing extracellular acidification in MCC cells. Our results demonstrate the effects of MCPyV ST on the cellular transcriptome and reveal that transformation is dependent, at least in part, on elevated aerobic glycolysis.

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer. However, it remains difficult to distinguish background, or 'passenger', cancer mutations from causal, or 'driver', mutations in these data sets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. Here we test the hypothesis that genomic variations and tumour viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways, such as Notch signalling and apoptosis, that go awry in cancer. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches increase the specificity of cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer.

First case report of endocarditis caused by haematobacter massiliensis in China.

BACKGROUND: Haematobacter massiliensis, a rare species of fastidious Gram-negative, non-motile, non-sporing, non-fermentative, pleomorphic, aerobic bacilli, has rarely been documented as the cause of infectious endocarditis in literature. Here we report the first case of infectious endocarditis (IE) caused by H. massiliensis in China. CASE PRESENTATION: A 44-year-old woman presented to the infectious department of Peking Union Medical College Hospital (Beijing) in August 2013, with a 7-week history of fevers, chills, sore throat, muscular soreness, occasional joint pain, and cough. The organism obtained by blood culture, identified as H. massiliensis by 16S rRNA gene sequencing, was finally implicated as the cause of infectious endocarditis. The patient was cured with amoxicillin/clavulanate combined with amikacin for 6 weeks. CONCLUSION: This is the first case report in China, of the isolation of H. massiliensis from the bloodstream of a patient with endocarditis. The microbiology and clinical study of the organism will help us understand it better in future clinical practice.

Identification and Antifungal Susceptibility Profile of Candida guilliermondii and Candida fermentati from a Multicenter Study in China.

With molecular sequencing as a gold standard, the Vitek MS, Bruker Biotyper MS, and Vitek-2 Compact systems correctly identified 92.7%, 97.0%, and 15.2% of 164 Candida guillermondii isolates, respectively, and none of 8 C. fermentati isolates. All of the isolates showed high susceptibility to echinocandins, but some C. guilliermondii isolates showed low azole susceptibility.

Identification and Antifungal Susceptibility Profiles of Candida haemulonii Species Complex Clinical Isolates from a Multicenter Study in China.

Candida haemulonii complex (Candida haemulonii, Candida haemulonii var. vulnera, and Candida duobushaemulonii) consists of emerging pathogens. Thirty-one isolates from 14 hospitals in China were studied for their species classification and antifungal susceptibilities. Performances of molecular (i.e., ribosomal DNA [rDNA] internal transcribed spacer [ITS] sequencing, D1/D2 sequencing, and ITS sequencer-based capillary gel electrophoresis [SCGE]) and phenotypic identification methods in species identification were compared. Twenty-six (83.9%) of 31 isolates were identified as C. haemulonii and 5 isolates were identified as C. duobushaemulonii by ITS sequencing as the reference method; results obtained by D1/D2 sequencing and ITS SCGE were concordant with those obtained by ITS sequencing for all (100%) of the isolates. All 31 isolates were identified as C. haemulonii by the Vitek matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system (bioMérieux, France), whereas the Bruker MS system (Bruker Daltoniks, Germany) correctly provided species identification for 77.4% and 100% of isolates using cutoff scores for species of ≥2.0 and ≥1.70, respectively. The Vitek 2 compact (bioMérieux) only identified 9 (29%) of 31 isolates. All isolates showed high MICs for amphotericin B (range, 2 to >8 µg/ml) and fluconazole (≥128 µg/ml) but low MICs (≤0.5 µg/ml) for the echinocandins. Our results reinforce the need for MALDI-TOF MS and/or molecular differentiation of species within the C. haemulonii complex. The multiresistant antifungal susceptibility profile of these isolates represents a challenge to therapy.

Malawi polyomavirus is a prevalent human virus that interacts with known tumor suppressors.

Malawi polyomavirus (MWPyV) is a recently identified human polyomavirus. Serology for MWPyV VP1 indicates that infection frequently occurs in childhood and reaches a prevalence of 75% in adults. The MWPyV small T antigen (ST) binds protein phosphatase 2A (PP2A), and the large T antigen (LT) binds pRb, p107, p130, and p53. However, the MWPyV LT was less stable than the simian virus 40 (SV40) LT and was unable to promote the growth of normal cells. This report confirms that MWPyV is a widespread human virus expressing T antigens with low transforming potential.

Intra-Genomic Internal Transcribed Spacer Region Sequence Heterogeneity and Molecular Diagnosis in Clinical Microbiology.

Internal transcribed spacer region (ITS) sequencing is the most extensively used technology for accurate molecular identification of fungal pathogens in clinical microbiology laboratories. Intra-genomic ITS sequence heterogeneity, which makes fungal identification based on direct sequencing of PCR products difficult, has rarely been reported in pathogenic fungi. During the process of performing ITS sequencing on 71 yeast strains isolated from various clinical specimens, direct sequencing of the PCR products showed ambiguous sequences in six of them. After cloning the PCR products into plasmids for sequencing, interpretable sequencing electropherograms could be obtained. For each of the six isolates, 10-49 clones were selected for sequencing and two to seven intra-genomic ITS copies were detected. The identities of these six isolates were confirmed to be Candida glabrata (n=2), Pichia (Candida) norvegensis (n=2), Candida tropicalis (n=1) and Saccharomyces cerevisiae (n=1). Multiple sequence alignment revealed that one to four intra-genomic ITS polymorphic sites were present in the six isolates, and all these polymorphic sites were located in the ITS1 and/or ITS2 regions. We report and describe the first evidence of intra-genomic ITS sequence heterogeneity in four different pathogenic yeasts, which occurred exclusively in the ITS1 and ITS2 spacer regions for the six isolates in this study.

Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities.

Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region.

Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.