Govaerts J, Goethals C, Van Breedam E
… +5 more, Sadzot-Delvaux C, Delputte P, Ogunjimi B, Lebrun M, Ponsaerts P
Microbiol Mol Biol Rev
· 2025 Sep · PMID 40767486
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SUMMARYWith varicella-zoster virus (VZV) being a strictly human-specific pathogen, cell culture models to study the VZV-host cell interactome predominantly rely on the use of primary human cells, immortalized cell lines...SUMMARYWith varicella-zoster virus (VZV) being a strictly human-specific pathogen, cell culture models to study the VZV-host cell interactome predominantly rely on the use of primary human cells, immortalized cell lines, and-more recently-stem cell-derived models. In this work, based on literature reports published within the past 15 years, we attempted to summarize major lessons learned from VZV research, with a specific focus on whether and how a variety of host cells respond upon VZV infection at the cellular level. Following this specific approach, we describe the cellular events occurring following VZV infection in a neural cell type context, an immune cell type context, and a skin cell type context. Highly relevant, and for sure subject to the development of future VZV research, cell types within each of the three compartments reviewed display similarities but also significant differences in cellular response to VZV infection. Clearly, these need further clarification on a cell-type and/or VZV strain-specific level. Finally, to increase physiological relevance, we propose an integrated approach for future VZV-host cell interactome studies on a systems level by using advanced human-induced pluripotent stem cell-derived skin, peripheral, and central nervous system compartments that can be complemented with an isogenic immune cell component. Combined with the implementation of state-of-the-art multi-omics analyses, as well as electrophysiological recordings, this next-generation toolbox for advanced virus-host cell interactome studies may help to elucidate important aspects of VZV biology, including the suggested link between VZV pathology and neurodegenerative diseases.
Microbiol Mol Biol Rev
· 2025 Sep · PMID 40626649
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SUMMARYThere is overwhelming evidence that antitumor CD8 T cell responses can mediate effective tumor control. CD8 T cell responses are quintessential defensive measures directed against categorically intracellular patho...SUMMARYThere is overwhelming evidence that antitumor CD8 T cell responses can mediate effective tumor control. CD8 T cell responses are quintessential defensive measures directed against categorically intracellular pathogens. It is thus intuitively obvious that viruses hold unique potential to mediate cancer in situ vaccination, the process whereby endogenous immune responses are provoked to empower antitumor immunity. Numerous attenuated viruses have been derived from diverse virus families and tested as intratumor "cancer virotherapies." However, the mechanistic understanding of how viruses mediate cancer in situ vaccination -including whether such attenuated viruses maintain the capacity to subvert antigen presentation and T cell priming, a common, defining feature of their wild-type precursors that may limit in situ vaccination, as well as the role of innate and adaptive antiviral immune responses in mediating overall therapy benefit-remains largely undefined. In this review, we provide a comprehensive overview of the molecular mechanisms, the unexpected benefit of profound attenuation, and the central role of both innate and adaptive antiviral immune responses in mediating polio virotherapy. In doing so, we aim to highlight the need for unraveling the enormous complexity and depth of virus:host interactions for devising rational strategies to leverage them for cancer immunotherapy.
Microbiol Mol Biol Rev
· 2025 Sep · PMID 40622160
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SUMMARYNeurotropic viruses, a diverse group of pathogens targeting the central nervous system (CNS), utilize multiple mechanisms to invade this highly protected compartment. These include hematogenous spread, retrograde...SUMMARYNeurotropic viruses, a diverse group of pathogens targeting the central nervous system (CNS), utilize multiple mechanisms to invade this highly protected compartment. These include hematogenous spread, retrograde axonal transport, and Trojan horse strategies, enabling viral entry and dissemination. Once within the CNS, these viruses interact with resident immune cells such as microglia and astrocytes, triggering type I interferon responses critical for antiviral defense. However, neurotropic viruses employ immune evasion strategies, including inhibition of pattern recognition receptors (PRRs), suppression of interferon signaling, and disruption of antigen presentation pathways, allowing them to evade immune detection. These tactics facilitate their productive replication within the CNS and, in some cases, lead to persistent infections, often resulting in severe neurological consequences such as encephalitis and neuronal damage. This review explores these dynamic interactions and emphasizes future research needs, particularly in understanding virus-host interactions and developing targeted therapeutics to combat these pathogens effectively.
Microbiol Mol Biol Rev
· 2025 Sep · PMID 40590533
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SUMMARYBacterial pathogens must navigate complex host environments to thrive, replicate, and ultimately transmit to new hosts. Effective transmission is critical for pathogen propagation and often requires overcoming hos...SUMMARYBacterial pathogens must navigate complex host environments to thrive, replicate, and ultimately transmit to new hosts. Effective transmission is critical for pathogen propagation and often requires overcoming host defenses and exploiting environmental conditions. The mechanisms used by bacterial pathogens to cause disease have been studied for decades, and numerous virulence factors have been identified and characterized through the use of genetic tools and animal models. While insightful, these discoveries have only scratched the surface of our understanding of disease mechanisms. Even less well understood is how pathogens move from an infected host to colonize and establish infection in a new host. Pathogens can move between hosts via direct and indirect modes, relying on numerous routes, such as respiratory, fecal-oral, direct contact, vector-borne, and vertical transmission. Recent advances in animal models for the study of bacterial transmission have enabled a more accurate recapitulation of transmission between humans. This review summarizes the current knowledge of bacterial transmission factors and animal models of transmission, and how these tools are advancing our understanding of the transmission mechanisms used by bacterial pathogens.
Microbiol Mol Biol Rev
· 2025 Sep · PMID 40539815
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SUMMARYPleomorphism in influenza viruses, characterized by diverse morphological forms ranging from spherical virions to elongated filaments, has been suggested to present significant implications for pathogenesis. This...SUMMARYPleomorphism in influenza viruses, characterized by diverse morphological forms ranging from spherical virions to elongated filaments, has been suggested to present significant implications for pathogenesis. This review examines the role of pleomorphism on the influenza virus life cycle, encompassing viral attachment and entry, replication, assembly, and budding, as well as transmission dynamics. It explores the determinants' underlying morphological variability in virions and their impact on viral fitness and host interactions. Insights into how pleomorphic forms of the virus influence disease severity and the efficacy of antivirals are discussed. Understanding the implications of pleomorphism in influenza virus pathogenesis is crucial for the development of effective disease prevention, control, and treatment strategies.
Santamaria-Castro I, Leiva-Rebollo R, Marín-Wong S
… +2 more, Jimenez-Guardeño JM, Ortega-Prieto AM
Microbiol Mol Biol Rev
· 2025 Sep · PMID 40503878
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SUMMARYThe mechanisms by which viruses enter host cells are crucial for their ability to infect and cause disease, serving as major targets for both host immune responses and therapeutic strategies. The severe acute resp...SUMMARYThe mechanisms by which viruses enter host cells are crucial for their ability to infect and cause disease, serving as major targets for both host immune responses and therapeutic strategies. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry process is primarily driven by the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor, in conjunction with the activity of endosomal cathepsin L and the serine protease transmembrane protease serine 2 (TMPRSS2). Nevertheless, recent scientific advances have expanded our understanding of SARS-CoV-2 entry mechanisms, uncovering alternative receptors and novel cofactors that may enhance viral tropism and adaptability. Given the critical role of the SARS-CoV-2 S protein in mediating host cell entry, it has become a primary target for prevention and therapeutic strategies. However, the continuous spread of SARS-CoV-2 has led to the emergence of S protein variants that may potentially confer a fitness advantage or modify key aspects of SARS-CoV-2 biology, such as transmissibility, infectivity, antigenicity, and/or pathogenicity, posing significant challenges to the efficacy of current interventions. In this review, we provide an updated and comprehensive overview of the latest advances in SARS-CoV-2 entry pathways and molecular mechanisms, exploring their implications for antiviral drug discovery, vaccine design, and the development of other biomedical strategies while addressing the challenges posed by the ongoing evolution of the virus.
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40434073
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SUMMARYThe bacterial cytoplasmic membrane, consisting of roughly equal proportions of proteins and lipids, plays a crucial role in cellular growth, metabolism, and maintaining the cytoplasmic boundary. It is a dynamic, f...SUMMARYThe bacterial cytoplasmic membrane, consisting of roughly equal proportions of proteins and lipids, plays a crucial role in cellular growth, metabolism, and maintaining the cytoplasmic boundary. It is a dynamic, fluid matrix that separates intracellular compartments, where lipids and proteins coexist in a highly organized yet flexible arrangement. Membrane fluidity, defined as the inverse of viscosity, determines how rapidly molecules diffuse within the membrane at a given temperature. This property is vital for protein mobility and biomolecular interactions. Structurally, the membrane primarily comprises a lamellar lipid bilayer, with glycerophospholipids and fatty acids forming its core framework. In , a key model organism for studying gram-positive bacterial physiology, major membrane lipids include phospholipids, glycolipids, and lipoteichoic acids, the latter anchored to diacylglycerol glycolipids. This review examines the synthesis and regulation of membrane lipids in , with a focus on fatty acid biosynthesis, its diversification, and post-synthetic modifications such as desaturation. It also explores the production of phosphatidic acid and the integration of fatty acid and phospholipid biosynthesis. We review the well-characterized pathway of cold-induced membrane lipid modification in , arguably the best-studied model system for temperature sensing. This pathway is tightly linked to transcriptional responses triggered by changes in bilayer viscosity, detected by a membrane-associated thermosensor. Finally, this review highlights the importance of fatty acid biosynthesis in differentiation and its contributions to the production of biotin and lipoic acid, two universal cofactors essential for fatty acid synthesis and intermediary metabolism.
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40340558
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SUMMARYOver the past 25 years, there has been an increasing number of mammalian (including human) infections caused by avian influenza A viruses that resulted in mild to severe illnesses. These viruses typically did not...SUMMARYOver the past 25 years, there has been an increasing number of mammalian (including human) infections caused by avian influenza A viruses that resulted in mild to severe illnesses. These viruses typically did not spread between mammals through aerosols in nature or in experimental settings. However, recently, this has changed, with several avian influenza A viruses exhibiting aerosol transmissibility among mammals, indicating that these viruses may pose a greater pandemic risk. In this review, we examine the current situation and discuss the mutations that may be necessary for avian influenza A viruses to efficiently replicate in mammals and transmit among them via aerosols.
Gillett DL, Selinidis M, Seamons T
… +11 more, George D, Igwe AN, Del Valle I, Egbert RG, Hofmockel KS, Johnson AL, Matthews KRW, Masiello CA, Stadler LB, Chappell J, Silberg JJ
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40197024
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SUMMARYEngineered microbes are being programmed using synthetic DNA for applications in soil to overcome global challenges related to climate change, energy, food security, and pollution. However, we cannot yet predict g...SUMMARYEngineered microbes are being programmed using synthetic DNA for applications in soil to overcome global challenges related to climate change, energy, food security, and pollution. However, we cannot yet predict gene transfer processes in soil to assess the frequency of unintentional transfer of engineered DNA to environmental microbes when applying synthetic biology technologies at scale. This challenge exists because of the complex and heterogeneous characteristics of soils, which contribute to the fitness and transport of cells and the exchange of genetic material within communities. Here, we describe knowledge gaps about gene transfer across soil microbiomes. We propose strategies to improve our understanding of gene transfer across soil communities, highlight the need to benchmark the performance of biocontainment measures , and discuss responsibly engaging community stakeholders. We highlight opportunities to address knowledge gaps, such as creating a set of soil standards for studying gene transfer across diverse soil types and measuring gene transfer host range across microbiomes using emerging technologies. By comparing gene transfer rates, host range, and persistence of engineered microbes across different soils, we posit that community-scale, environment-specific models can be built that anticipate biotechnology risks. Such studies will enable the design of safer biotechnologies that allow us to realize the benefits of synthetic biology and mitigate risks associated with the release of such technologies.
Tarracchini C, Lordan C, Milani C
… +14 more, Moreira LPD, Alabedallat QM, de Moreno de LeBlanc A, Turroni F, Lugli GA, Mancabelli L, Longhi G, Brennan L, Mahony J, LeBlanc JG, Nilaweera KN, Cotter PD, van Sinderen D, Ventura M
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40172109
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SUMMARYIn recent years, exhaustive efforts have been made to dissect the composition of gut-associated microbial communities and associated interactions with their human host, which are thought to play a crucial role in...SUMMARYIn recent years, exhaustive efforts have been made to dissect the composition of gut-associated microbial communities and associated interactions with their human host, which are thought to play a crucial role in host development, physiology, and metabolic functions. Although such studies were initially focused on the description of the compositional shifts in the microbiota that occur between different health conditions, more recently, they have provided key insights into the functional and metabolic contributions of the gut microbiota to overall host physiology. In this context, an important metabolic activity of the human gut microbiota is believed to be represented by the synthesis of various vitamins that may elicit considerable benefits to human health. A growing body of scientific literature is now available relating to (predicted) bacterial vitamin biosynthetic abilities, with ever-growing information concerning the prevalence of these biosynthetic abilities among members of the human microbiota. This review is aimed at disentangling if and how cooperative trophic interactions of human microbiota members contribute to vitamin production, and if such, gut microbiota-mediated vitamin production varies according to different life stages. Moreover, it offers a brief exploration of how different diets may influence vitamin production by shaping the overall composition and metabolic activity of the human gut microbiota while also providing preliminary insights into potential correlations between human microbiota-associated vitamin production and the occurrence of human diseases and/or metabolic disorders.
Whitfield C, Kelly SD, Stanton TD
… +4 more, Wyres KL, Clarke BR, Forrester TJB, Kowalczyk A
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40116577
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SUMMARY is a gram-negative species, whose isolates are found in the environment and as commensals in the human gastrointestinal tract. This bacterium is among the leading causes of a range of nosocomial and community-acq...SUMMARY is a gram-negative species, whose isolates are found in the environment and as commensals in the human gastrointestinal tract. This bacterium is among the leading causes of a range of nosocomial and community-acquired infections, particularly in immunocompromised individuals, where it can give rise to pneumonia, urinary tract infections, septicemia, and liver abscesses. Treatment of infections is compromised by the emergence of isolates producing carbapenemase and extended-spectrum β-lactamase enzymes, making it a high priority for new therapeutic approaches including vaccination and immunoprophylaxis. One potential target for these strategies is the O-antigen polysaccharide component of lipopolysaccharides, which are important virulence determinants for . Consideration of immunotherapeutic opportunities requires a comprehensive and fundamental understanding of O-polysaccharide structures, distribution of particular O serotypes in clinical isolates, and the potential for antigenic diversification. The number of recognized O-polysaccharide antigens has varied over time, complicated by the observation that some examples share similar structural (and potentially antigenically cross-reactive) elements, and by the existence of genetic loci for which corresponding O-polysaccharide structures have yet to be determined. Here, we provide a comprehensive integration of the current carbohydrate structures and genetic information, together with a proposal for an updated classification system for O-antigens, that is being implemented in Kaptive for molecular serotyping. The accumulated insight into O-polysaccharide assembly pathways is used to describe the molecular basis for O-antigen diversity in .
Carlier Y, Dumonteil E, Herrera C
… +5 more, Waleckx E, Tibayrenc M, Buekens P, Truyens C, Muraille E
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40116484
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SUMMARYChagas disease (CD) is caused by the protozoan parasite (Tc), infecting 6-7 million people. It is transmitted by insect vectors, orally, through infected tissues, or congenitally. Tc infection can progress toward...SUMMARYChagas disease (CD) is caused by the protozoan parasite (Tc), infecting 6-7 million people. It is transmitted by insect vectors, orally, through infected tissues, or congenitally. Tc infection can progress toward chronic cardiac and/or digestive severe and fatal CD in 20%-40% of patients. Tc exhibits an important genetic and phenotypic intraspecies diversity and a preponderant clonal population structure. The impact of multiclonal coinfections has been little studied in CD patients. Relationships between the currently used discrete typing unit (DTU)-based classification of Tc lineages and the occurrence of the different clinical forms of CD, its congenital transmission, as well as the efficacy of trypanocidal molecules (benznidazole and nifurtimox) could not be established. In this review, we revisit the different aspects of Tc diversity and analyze the impact of infections with multiple clones and their variants on the dynamic and pathogenesis of CD and its maternal-fetal transmission. We propose to call "cruziome" all the Tc clones and their variants infecting a given host and provide strong evidence that (i) multiclonal Tc infections are likely the rule rather than the exception; (ii) each "cruziome" is associated with a unique combination of virulence factors, tissular tropisms, and host immune responses; (iii) accordingly, some particularly harmful "cruziomes" likely trigger the occurrence and progression of CD and might also favor the congenital transmission of parasites. We propose that our concept of "cruziome" should be taken into consideration because of its practical consequences in epidemiological studies, laboratory diagnosis, clinical management, and treatment of CD.
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40111037
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SUMMARYGut microbes provide benefits to some animals, but their distribution and effects across diverse hosts are still poorly described. There is accumulating evidence for host specificity (i.e., a pattern where differe...SUMMARYGut microbes provide benefits to some animals, but their distribution and effects across diverse hosts are still poorly described. There is accumulating evidence for host specificity (i.e., a pattern where different microbes tend to associate with distinct host lineages), but the causes and consequences of this pattern are unclear. Combining experimental tests in the laboratory with broad surveys in the wild is a promising approach to gaining a comprehensive and mechanistic understanding of host specificity prevalence, origin, and importance. Social bees represent an ideal testbed for this endeavor because they are phylogenetically and functionally diverse, with host-specific, stable, and tractable gut microbiota. Furthermore, the western honeybee () is an emerging experimental model system for studying microbiota-host interactions. In this review, we summarize data on the prevalence and strength of host specificity of the social bee gut microbiota (bumblebees, stingless bees, and honeybees), as well as the potential and proven ecological and molecular mechanisms that maintain host specificity. Overall, we found that host specificity in bees is relatively strong and likely results from several processes, including host filtering mediated by the immune system and priority effects. However, more research is needed across multiple social bee species to confirm these findings. To help future research, we summarize emerging hypotheses in the field and propose several experimental and comparative tests. Finally, we conclude this review by highlighting the need to understand how host specificity can influence host health.
Microbiol Mol Biol Rev
· 2025 Jun · PMID 40084887
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SUMMARYThe human microbiome, including bacteria, fungi, archaea, and viruses, is intimately linked to both health and disease. The relationship between bacteria and disease has received much attention and intensive inves...SUMMARYThe human microbiome, including bacteria, fungi, archaea, and viruses, is intimately linked to both health and disease. The relationship between bacteria and disease has received much attention and intensive investigation, while that of the fungal microbiome, also known as mycobiome, has lagged far behind bacteria. There is growing evidence showing mycobiome dysbiosis in cancer patients, and certain cancer-specific fungi may contribute to cancer progression by interacting with both host and bacteria. It was also demonstrated that the role of fungi-derived products in cancer should also not be underestimated. Therefore, investigating how fungal pathogenesis contributes to the onset and spread of cancer would yield crucial information for cancer diagnosis, prevention, and anti-cancer therapy.
Blader I, Goodrum F, Imperiale MJ
… +17 more, Casadevall A, Arias CA, Baumler A, Burnham C-AD, Cuomo CA, Detweiler CS, Forrest GN, Gilbert JA, Lovett S, Maloy S, McAdam A, Newton I, Reguera G, O'Toole GA, Schloss PD, Shade A, Whiteley M
Microbiol Mol Biol Rev
· 2025 Mar · PMID 40013872
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Kordana N, Johnson A, Quinn K
… +2 more, Obar JJ, Cramer RA
Microbiol Mol Biol Rev
· 2025 Mar · PMID 39927770
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SUMMARYAdvances in modern medical therapies for many previously intractable human diseases have improved patient outcomes. However, successful disease treatment outcomes are often prevented due to invasive fungal infecti...SUMMARYAdvances in modern medical therapies for many previously intractable human diseases have improved patient outcomes. However, successful disease treatment outcomes are often prevented due to invasive fungal infections caused by the environmental mold . As contemporary antifungal therapies have not experienced the same robust advances as other medical therapies, defining mechanisms of disease initiation and progression remains a critical research priority. To this end, the World Health Organization recently identified as a research priority human fungal pathogen and the Centers for Disease Control has highlighted the emergence of triazole-resistant isolates. The expansion in the diversity of host populations susceptible to aspergillosis and the complex and dynamic genotypic and phenotypic diversity call for a reinvigorated assessment of aspergillosis pathobiological and drug-susceptibility mechanisms. Here, we summarize recent advancements in the field and discuss challenges in our understanding of heterogeneity and its pathogenesis in diverse host populations.
Microbiol Mol Biol Rev
· 2025 Mar · PMID 39927764
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Pathogens must acquire essential nutrients to successfully colonize and proliferate in host tissue. Additionally, nutrients provide signals that condition pathogen deployment of factors that promote disease. A series of...Pathogens must acquire essential nutrients to successfully colonize and proliferate in host tissue. Additionally, nutrients provide signals that condition pathogen deployment of factors that promote disease. A series of transcriptomics experiments over the last 20 years, primarily with and to a lesser extent with , provide insights into the nutritional requirements for proliferation in host tissues. Notably, the identified functions include a number of transporters for key nutrients including sugars, amino acids, metals, and phosphate. Here, we first summarize the gene expression studies and then discuss the follow-up analyses that specifically test the relevance of the identified transporters for the ability of the pathogens to cause disease. The conclusion is that predictions based on transcriptional profiling of cryptococcal cells in infected tissue are well supported by subsequent investigations using targeted mutations. Overall, the combination of transcriptomic and genetic approaches provides substantial insights into the nutritional requirements that underpin proliferation in the host.
Microbiol Mol Biol Rev
· 2025 Mar · PMID 39868790
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SUMMARYHuman papillomaviruses (HPVs) are small DNA viruses that are responsible for significant disease burdens worldwide, including cancers of the cervix, anogenital tract, and oropharynx. HPVs infect stratified epithel...SUMMARYHuman papillomaviruses (HPVs) are small DNA viruses that are responsible for significant disease burdens worldwide, including cancers of the cervix, anogenital tract, and oropharynx. HPVs infect stratified epithelia at a variety of body locations and link their productive life cycles to the differentiation of the host cell. These viruses have evolved sophisticated mechanisms to exploit cellular pathways, such as DNA damage repair (DDR), to regulate their life cycles. HPVs activate key DDR pathways such as ATM, ATR, and FA, which are critical for maintaining genomic integrity but are often dysregulated in cancers. Importantly, these DDR pathways are essential for HPV replication in undifferentiated cells and amplification upon differentiation. The ability to modulate these DDR pathways not only enables HPV persistence but also contributes to cellular transformation. In this review, we discuss the recent advances in understanding the mechanisms by which HPV manipulates the host DDR pathways and how these depend upon enhanced topoisomerase activity and R-loop formation. Furthermore, the strategies to manipulate DDR pathways utilized by high-risk HPVs are compared with those used by other DNA viruses that exhibit similarities and distinct differences.