Biology subjects

Grey, F.

Publications and source records attributed to Grey, F..

14 recordsLinked to original sources

bioRxiv2026

A genome-wide CRISPR knockout screen identifies host dependency factors and potential viral-induced cell death regulators for porcine deltacoronavirus infection

Porcine deltacoronavirus (PDCoV) is a globally circulating coronavirus of swine that causes severe enteric disease and mortality in neonatal piglets. Its broad host range and zoonotic potential raises concerns about continued spillover into human populations. However, the host factors that govern PDCoV infection remain largely unexplored. Identifying host factors involved in virus infection may uncover novel therapeutic targets for antiviral drug development or targets for gene editing to create resistant pigs. Here, we conducted a genome-wide CRISPR knockout (GeCKO) screen to identify host factors contributing to PDCoV infection in swine testicular (ST) cells. Small guide RNAs (sgRNAs) targeting the ANPEP gene, expressing the main receptor porcine aminopeptidase N for PDCoV, were enriched in PDCoV-resistant cells, demonstrating the validity of the screen. Moreover, we identified transmembrane protein 30A (TMEM30A), an accessory {beta}-subunit of the P4-ATPase flippase complex, as a host dependency factor for PDCoV infection along with several potential PDCoV-induced cell death regulators, including DET1, IFNAR1, RFWD2, STAT1 and TP53. We further demonstrated that PDCoV attachment and internalization into cells were significantly impaired in TMEM30A knockout ST cells, suggesting that TMEM30A is important in the early stages of the PDCoV life cycle. Because TMEM30A also contributes to SARS-CoV-2 replication, future studies are warranted to investigate its mechanistic role in the context of coronavirus infection.

molecular biology↗

bioRxiv2026

Suidae iPSC-derived macrophages as models for investigating susceptibility and resilience to African swine fever virus

African swine fever virus (ASFV) causes a lethal haemorrhagic fever in pigs and spread of this disease threatens many pig species (Suidae) globally. By contrast, ASFV infections in the natural evolved hosts, the warthog and bushpig, are subclinical. The macrophage (M{varphi}) is the primary target of ASFV and species-dependent responses in M{varphi}s are presumed to influence disease susceptibility. In an attempt to model these differences in vitro, we generated transgene-regulated induced pluripotent stem cells (iPSCs) from domestic pig, wild boar, red river hog and warthog, and confirmed that their corresponding iPSC-derived M{varphi}s (iPSCdMs) supported infection and replication of ASFV. In contrast to the other species, however, warthog iPSCdMs did not induce interferon upon infection by either virulent or attenuated ASFV. iPSCdMs may therefore represent an experimental system to understand how ASFV infection of M{varphi}s contributes to disease and aid development of strategies to combat this economically and environmentally devastating pathogen.

developmental biology↗

bioRxiv2026

cGAS activation during human cytomegalovirus infection is driven by exogenous DNA

Type I interferon (IFN) induction is a central component of the innate immune response to viral infection, and the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) has been identified as a key mediator of IFN production during human cytomegalovirus (HCMV) infection. However, how cGAS detects HCMV remains unresolved, as the viral genome is encapsidated and trafficked directly to the nucleus, limiting cytoplasmic exposure. Here, we show that IFN induction during HCMV infection of primary fibroblast cells is predominantly driven by cGAS recognition of exogenous DNA present in standard laboratory virus preparations rather than the encapsidated viral genome. DNase treatment of AD169 and low-passage TB40/E-GFP viral stocks substantially reduced total DNA content without affecting infectivity, yet markedly abrogated IFN induction, IFN-stimulated gene expression and IRF3 nuclear translocation. Immunofluorescence analysis further revealed cytoplasmic accumulation of DNA in cells infected with untreated virus stocks, which was absent following DNase treatment. Together, these findings demonstrate that contaminating DNA in viral preparations is sufficient to activate cGAS and drive IFN responses during HCMV infection in vitro, highlighting a critical confounding factor in studies of innate immune sensing. Author SummaryHuman cytomegalovirus (HCMV) is a common herpesvirus that establishes lifelong infection and can cause serious disease in immunocompromised individuals and newborns. When cells detect viral infection, they produce type I interferons (IFNs), antiviral molecules that help limit virus spread. Previous studies have suggested that HCMV is sensed by a cellular DNA sensor called cGAS, which detects viral DNA in the cytoplasm and triggers IFN production. However, how cGAS gains access to the HCMV genome has remained unclear, because the viral DNA is enclosed within a protective capsid and transported directly to the nucleus during infection. In this study, we show that most IFN production observed during HCMV infection of fibroblast cells in vitro is driven not by sensing of the viral genome itself, but by contaminating DNA present in standard laboratory virus preparations. Treating virus stocks with DNase to remove this exogenous DNA abolished IFN induction without affecting viral infectivity. These findings highlight the importance of controlling for exogenous nucleic acids when interpreting how host cells detect viral infection.

microbiology↗

bioRxiv2025

Identification of key host genes for influenza A virus in avian cells using a genome-wide CRISPR-Cas9 screen

Influenza A virus (IAV) causes major economic losses to the poultry industry and poses a zoonotic threat to human health. Potential pandemic outbreaks are underpinned by the ability of the virus to jump from one species to another. Host-virus interactions can dictate the success of such events and while systematic studies have successfully mapped host virus interactions in human cells, few studies have been performed in relevant animal host cell lines. Here, we conducted two independent genome-wide CRISPR/Cas9 knockout screens in chicken lung epithelial cells infected with either the human-adapted PR8 vaccine strain or the avian UDL 3:5 reassortant virus encoding PR8 HA, NA and M segments. Rather than selecting solely for cell survival, we used anti-M2 antibody staining and fluorescence-activated cell sorting to capture host factors influencing multiple stages of the IAV life cycle. Across both screens, we identified 104 genes required for efficient replication in chicken cells, including 16 with strong effects (log2 fold change > 2). Comparative analysis with published human screens revealed 17 conserved host factors, 19 human-specific factors, and 42 chicken-specific factors, highlighting potential species-specific interactions. Top hits included genes involved in sialic acid biosynthesis and N-linked glycosylation--SLC35A1, SLC35A2, and the avian-specific influenza polymerase cofactor ANP32A. Functional validation demonstrated that MOGS, MGAT1, DENR, DMXL1, ENO1, IPO9, KLF6, PTAR1, and TSG101 contribute to multiple stages of the IAV life cycle. In particular, MOGS and MGAT1 were essential for N-glycan processing and modulated cell-surface sialic acid abundance, with strain- and species-specific effects. These findings define a genetic landscape of IAV dependency factors in chicken cells and suggest shared and species-specific host requirements that could impact cross-species transmission.

cell biology↗

bioRxiv2024

Cas10 based 7SL-sRNA diagnostic for the detection of active trypanosomiasis

Animal Trypanosomosis (AT) is a significant disease affecting cattle across sub-Saharan Africa, Latin America, and Asia, posing a major threat to economic productivity and animal welfare. The absence of reliable diagnostic tests has led to an over-reliance on widespread pre-emptive drug treatments, which not only compromise animal health but also heighten the risk of drug resistance. The chronic nature of AT, characterized by cyclical low or undetectable parasite levels, and the necessity for field-applicable tests that can distinguish between active infection and prior exposure, present considerable challenges in developing effective diagnostics. In previous work, we identified a parasite-specific small RNA, 7SL-sRNA, which is detectable in the serum of infected cattle, even during the chronic stages of infection. However, existing methods for detecting sRNA require specialized equipment, making them unsuitable for field use. In this study, we have developed a lateral flow diagnostic test utilizing Cas10 technology for the detection of 7SL-sRNA. This assay demonstrates high sensitivity and specificity, effectively identifying active infections in cattle, including during chronic phases (with positive signals observed up to the 63 days post-infection end point). This is the first instance of Cas10 being used for small RNA detection, paving the way for a cost-effective, user-friendly, and field-deployable diagnostic test for AT, while establishing Cas10 technology for the detection of small RNAs in general. Author summaryAnimal Trypanosomosis (AT) is a parasitic disease that affects livestock, causing major economic losses and harm to animal health. Cheap effective diagnostics that can be easily used in the field would have a major impact on the disease burden by enabling better treatment practices. However, parasites causing the disease - trypanosomes - are often undetectable via conventional methods, especially during chronic disease stages. More accurate diagnostics are not suitable for use in the field and are therefore unavailable to farmers. This has led to the overuse of drug treatments that can harm animals and lead to the emergence of drug resistance. We previously discovered a trypanosome-specific small RNA, called 7SL-sRNA, that can be detected in the blood of infected cattle, even during the chronic stages of AT when parasites are not visible via microscopy. However, detecting this RNA has required complex equipment, limiting its use in field settings. Building on this work, we have now developed a field applicable test for trypanosomosis that uses Cas10 technology to detect 7SL-sRNA via a simple lateral flow assay. This test is easy to use and accurately identifies active infections, including during the chronic phase of the disease. This is the first time Cas10 technology has been used to detect small RNAs, offering a promising, cost-effective tool for diagnosing AT and potentially other neglected parasitic diseases.

microbiology↗

bioRxiv2022

Zoonotic avian influenza viruses evade human BTN3A3 restriction

Cross-species transmission of avian influenza A viruses (IAVs) into humans could represent the first step of a future pandemic1. Multiple factors limiting the spillover and adaptation of avian IAVs in humans have been identified, but they are not sufficient to explain which virus lineages are more likely to cross the species barrier1,2. Here, we identified human BTN3A33 (butyrophilin subfamily 3 member A3) as a potent inhibitor of avian but not human IAVs. We determined that BTN3A3 is constitutively expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts at the early stages of virus replication by inhibiting avian IAV vRNA transcription. We identified residue 313 in the viral nucleoprotein (NP) as the genetic determinant of BTN3A3 sensitivity (313F, or rarely 313L in avian viruses) or evasion (313Y or 313V in human viruses). However, several serotypes of avian IAVs that spilled over into humans in recent decades evade BTN3A3 restriction. In these cases, BTN3A3 evasion is due to substitutions (N, H or Q) in NP residue 52 that is adjacent to residue 313 in the NP structure4. Importantly, we identified more than 150 avian IAV lineages with a BTN3A3-resistant genotype. In conclusion, sensitivity or resistance to BTN3A3 is another factor to consider in the risk assessment of the zoonotic potential of avian influenza viruses.

microbiology↗

bioRxiv2022

CpG enrichment as a vaccine strategy for influenza A virus

Synonymous recoding of RNA virus genomes is a promising approach for generating attenuated viruses to use as vaccines. Problematically, recoding typically hinders virus growth, but this may be rectified using CpG dinucleotide enrichment. CpGs are recognised by cellular zinc-finger antiviral protein (ZAP), and so in principle, removing ZAP sensing from a virus propagation system will reverse attenuation of a CpG-enriched virus, enabling high titre yield of a vaccine virus. We tested this using a vaccine strain of influenza A virus (IAV) engineered for increased CpG content in genome segment 1. Virus attenuation was mediated by the short isoform of ZAP, correlated with the number of CpGs added, and was enacted via turnover of viral transcripts. The CpG-enriched virus was strongly attenuated in mice, yet conveyed protection from a potentially lethal challenge dose of wildtype virus. Importantly for vaccine development, CpG-enriched viruses were genetically stable during serial passage. Unexpectedly, in both MDCK cells and embryonated hens eggs that are used to propagate live attenuated influenza vaccines, the ZAP-sensitive virus was fully replication competent. Thus, ZAP- sensitive CpG enriched viruses that are defective in human systems can yield high titre in vaccine propagation systems, providing a realistic, economically viable platform to augment existing live attenuated vaccines. AUTHOR SUMMARYCpG dinucleotides are under-represented in vertebrate genomes, wherein cytosines in the CpG conformation are methylated to regulate transcription. Methylated cytosines are prone to deamination, resulting in TpG dinucleotides replacing CpGs. The resultant CpG suppression has provided a route by which vertebrate cells can recognise RNA from invading pathogens, using cellular Zinc-finger Antiviral Protein (ZAP) as a CpG sensor. Vertebrate-infecting RNA viruses also genomically suppress CpGs, and it is believed that this is an evolved trait to evade detection by ZAP. Here, we engineered an influenza A virus (IAV) with elevated CpG content and characterised how this impacts viral replication. CpG addition resulted in viral attenuation, mediated by ZAP activity. CpG suppression is conserved in dog and chicken genomes (relevant for live attenuated IAV vaccine propagation), and it is logical to predict that ZAP-mediated CpG sensing would also be conserved in these species. However, when we propagated ZAP-sensitive IAV in cognate culture systems, we saw no replication defect. This unexpected result raises questions about why viruses infecting these species suppress CpG in their genomes, and importantly delivers a new, tractable approach to augment rational live attenuated IAV vaccine design.

microbiology↗

bioRxiv2021

Jaagsiekte sheep retrovirus infection induces changes in microRNA expression in the ovine lung

Ovine pulmonary adenocarcinoma (OPA) is an infectious neoplastic lung disease of sheep caused by jaagsiekte sheep retrovirus. OPA is an important veterinary problem and is also a valuable large animal model for human lung adenocarcinoma. JSRV infects type 2 alveolar epithelial cells in the lung and induces the growth of tumors, but little is known about the molecular events that lead to the activation of oncogenic pathways in infected cells. MicroRNAs (miRNAs) are small RNA molecules of approximately 22 nucleotides with important roles in regulating gene expression in eukaryotes and with well-established roles in cancer. Here we used small-RNA sequencing to investigate the changes in miRNA expression that occur in JSRV-infected ovine lung. After filtering out low abundance miRNAs, we identified expression of 405 miRNAs, 32 of which were differentially expressed in JSRV-infected lung compared to mock-inoculated control lung. Highly upregulated miRNAs included miR-182, miR-183, miR-96 and miR-135b, which have also been associated with oncogenic changes in human lung cancer. Network analysis of genes potentially targeted by the deregulated miRNAs identified their involvement in pathways known to be dysregulated in OPA. We found no evidence to support the existence of miRNAs encoded by JSRV. This study provides the first information on miRNA expression in OPA and identifies a number of targets for future studies into the role of these molecules in the pathogenesis of this unique veterinary model for human lung adenocarcinoma. IMPORTANCEOvine pulmonary adenocarcinoma is a neoplastic lung disease of sheep caused by jaagsiekte sheep retrovirus (JSRV). OPA is a significant welfare and economic concern for sheep producers and is a valuable large animal model for human lung adenocarcinoma. MicroRNAs are small RNA molecules of approximately 22 nucleotides with important functions in regulating gene expression in eukaryotes and with well-established roles in cancer. In this study, we examined the changes in microRNA expression that occur in the lung in response to JSRV infection. We identified differential expression of a number of host-encoded microRNAs in infected tissue, including microRNAs with roles in human cancer. We found no evidence that JSRV encodes a microRNA. This study provides new insights on the cellular response to JSRV infection in the ovine lung, which will inform future studies into the pathogenesis of OPA in sheep and its use as a model for human lung adenocarcinoma.

microbiology↗

bioRxiv2021

Stem cell-derived macrophages as a new platform for studying host-pathogen interactions in livestock

Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. We explored how pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages from livestock. Porcine and bovine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages. Pig PSCdMs were productively infected by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and African Swine Fever Virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, Pig PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied in parental stem cells, or directly by lentiviral vector transduction. PSCs and differentiated derivatives therefore provide a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in livestock.

immunology↗

bioRxiv2020

Cytomegaloviral determinants of CD8+ T cell programming and RhCMV/SIV vaccine efficacy

Simian immunodeficiency virus (SIV) insert-expressing, 68-1 Rhesus Cytomegalovirus (RhCMV/SIV) vectors elicit major histocompatibility complex (MHC)-E- and -II-restricted, SIV-specific CD8+ T cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against SIV challenge in the rhesus monkeys (RMs) has not been characterized. We demonstrate that these unconventional responses resulted from a chance genetic rearrangement in 68-1 RhCMV that abrogated the function of eight distinct immunomodulatory gene products encoded in two RhCMV genomic regions (Rh157.5/.4 and Rh158-161). Differential repair of these genes with either RhCMV-derived or orthologous human CMV (HCMV)-derived sequences (UL128/130; UL146/147) leads to either of two distinct CD8+ T cell response types - MHC-Ia-restricted-only, or a mix of MHC-II- and MHC-Ia-restricted CD8+ T cells. Despite response magnitude and functional differentiation being similar to RhCMV 68-1, neither alternative response type mediated protection against SIV challenge. These findings implicate MHC-E-restricted CD8+ T cell responses as mediators of anti-SIV efficacy and indicate that translation of RhCMV/SIV vector efficacy to humans will likely require deletion of all the genes that inhibit these responses from the HCMV/HIV vector. One-sentence summaryEight genes in two spatially distinct RhCMV gene regions control induction of unconventionally restricted CD8+ T cell responses and the efficacy of RhCMV/SIV vaccine vectors against SIV challenge.

immunology↗

bioRxiv2020

Intra-genome variability in the dinucleotide composition of SARS-CoV-2

CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. Artificial modification of CpG frequency is a valid approach for live attenuated vaccine development, and if this is to be applied to SARS-CoV-2, we must first understand the role CpG motifs play in regulating SARS-CoV-2 replication. Accordingly, the CpG composition of the newly emerged SARS-CoV-2 genome was characterised in the context of other coronaviruses. CpG suppression amongst coronaviruses does not significantly differ according to genera of virus, but does vary according to host species and primary replication site (a proxy for tissue tropism), supporting the hypothesis that viral CpG content may influence cross-species transmission. Although SARS-CoV-2 exhibits overall strong CpG suppression, this varies considerably across the genome, and the Envelope (E) open reading frame (ORF) and ORF10 demonstrate an absence of CpG suppression. While ORF10 is only present in the genomes of a subset of coronaviruses, E is essential for virus replication. Across the Coronaviridae, E genes display remarkably high variation in CpG composition, with those of SARS and SARS-CoV-2 having much higher CpG content than other coronaviruses isolated from humans. Phylogeny indicates that this is an ancestrally-derived trait reflecting their origin in bats, rather than something selected for after zoonotic transfer. Conservation of CpG motifs in these regions suggests that they have a functionality which over-rides the need to suppress CpG; an observation relevant to future strategies towards a rationally attenuated SARS-CoV-2 vaccine.

evolutionary biology↗

bioRxiv2020

Human cytomegalovirus evades ZAP detection by suppressing CpG dinucleotides in the major immediate early genes.

The genomes of RNA and small DNA viruses of vertebrates display significant suppression of CpG dinucleotide frequencies. Artificially increasing dinucleotide frequencies results in substantial attenuation of virus replication, suggesting that these compositional changes may facilitate recognition of non-self RNA sequences. Recently, the interferon inducible protein ZAP, was identified as the host factor responsible for sensing CpG in viral RNA, through direct binding and possibly downstream targeting for degradation. Using an arrayed interferon stimulated gene expression library screen, we identified ZAPS, and its associated factor TRIM25, as direct inhibitors of human cytomegalovirus (HCMV) replication. Exogenous expression of ZAPS and TRIM25 significantly reduced virus replication while knockdown resulted in increased virus replication. HCMV displays a strikingly heterogeneous pattern of CpG representation with a specific suppression of CpGs within the IE1 major immediate early transcript which is absent in subsequently expressed genes. We demonstrated that suppression of CpG dinucleotides in the IE1 gene allows evasion of inhibitory effects of ZAP. During HCMV infection, expression of ZAP and TRIM25 are rapidly reduced, removing pressure to suppress dinucleotide frequencies in viral genes expressed after the immediate early genes, while acute virus replication and high levels of ZAP are mutually exclusive. Finally, we show that TRIM25 regulates alternative splicing between the ZAP short and long isoforms during HCMV infection and interferon induction, with knockdown of TRIM25 resulting in decreased ZAPS and corresponding increased ZAPL expression. These results demonstrate for the first time that ZAP is a potent host restriction factor against large DNA viruses and that HCMV evades ZAP detection through suppression of CpG dinucleotides within the major immediate early transcripts. Furthermore, TRIM25 is required for efficient upregulation of the interferon inducible short isoform of ZAP through regulation of alternative splicing.

microbiology↗

bioRxiv2019

Asparagine deprivation causes a reversible inhibition of Human Cytomegalovirus acute virus replication

As obligate intracellular pathogens, viruses rely on the host cell machinery to replicate efficiently, with the host metabolism extensively manipulated for this purpose. High throughput siRNA screens provide a systematic approach for the identification of novel host-virus interactions. Here, we report a large-scale screen for host factors important for human cytomegalovirus (HCMV), consisting of 6,881 siRNAs. We identified 47 proviral factors and 68 antiviral factors involved in a wide range of cellular processes including the mediator complex, proteasome function and mRNA splicing. Focused characterisation of one of the hits, asparagine synthetase (ASNS), demonstrated a strict requirement for asparagine for HCMV replication which leads to an early block in virus replication before the onset of DNA amplification. This effect is specific to HCMV, as knockdown of ASNS had little effect on herpes simplex virus-1 or influenza A virus replication, suggesting the restriction is not simply due to a failure in protein production. Remarkably, virus replication could be completely rescued seven days post-infection with addition of exogenous asparagine, indicating that while virus replication is restricted at an early stage, it maintains the capacity for full replication days after initial infection. This study represents the most comprehensive siRNA screen for the identification of host factors involved in HCMV replication and identifies the non-essential amino acid, asparagine as a critical factor in regulating HCMV virus replication. These results have implications for control of viral latency and the clinical treatment of HCMV in patients.\n\nImportanceHCMV accounts for more than 60% of complications associated with solid organ transplant patients. Prophylactic or preventative treatment with antivirals, such as ganciclovir, reduces the occurrence of early onset HCMV disease. However, late onset disease remains a significant problem and prolonged treatment, especially in patients with suppressed immune systems, greatly increases the risk of antiviral resistance. Very few antivirals have been developed for use against HCMV since the licensing of ganciclovir, and of these, the same viral genes are often targeted, reducing the usefulness of these drugs against resistant strains. An alternative approach is to target host genes essential for virus replication. Here we demonstrate that HCMV replication is highly dependent on levels of the amino acid asparagine and knockdown of a critical enzyme involved in asparagine synthesis results in severe attenuation of virus replication. These results suggest that reducing asparagine levels through dietary restriction or chemotherapeutic treatment could limit HCMV replication in patients.

microbiology↗

bioRxiv2019

NK cells force cytomegalovirus to use hematopoietic cells and immune evasion for dissemination after mucosal infection

Cytomegalovirus (CMV) infects most people in the world and causes clinically important disease in immune compromised and immune immature individuals. How the virus disseminates from the initial site of infection is poorly understood. We used an innovative approach, involving insertion of target sites for the haematopoietic specific miRNA miR-142-3p into an essential viral gene in murine cytomegalovirus. This virus was unable to disseminate to the salivary gland following intranasal infection, demonstrating a strict need for hematopoietic cells for dissemination from the natural site of infection. Viral immune evasion genes that modulate MHC-I expression and NKG2D activation were also required in this setting, as MCMV lacking these genes exhibited impaired dissemination of the viral genome to the salivary gland, and there was no detectable viral replication in the salivary gland. Depletion of T cells rescued the replication of this evasion-deficient virus in the salivary gland. Surprisingly however, the early dissemination to the salivary gland of this evasion-deficient virus, could be rescued by depletion of NK cells, but not T cells. These data are the first to show a profound loss of MCMV fitness in the absence of its MHC-I evasion genes and suggest that they protect the virus from NK cells during hematopoietic dissemination to the salivary gland, where they continued to need the three evasion genes to avoid T cell responses. Remarkably, we found that depletion of NK cells also freed the virus from the need to infect hematopoietic cells in order to reach the salivary gland. Thus, our data show that MCMV adapts to NK cell pressure after intranasal infection by using hematopoietic cells for dissemination while immune evasion genes protect the virus from NK cells during dissemination and from T cells within mucosal tissues.

immunology↗