Reviews in Medical Virology最新文献

Dengue virus (DENV) and Monkeypox virus (MPXV) are two major re-emerging viral pathogen, which have recently gained global attention, mainly in light of their potential for widespread transmission and the ability to cause various complications. While the characteristic manifestations of these infections comprise lymphadenopathy, fever, and rash, recent studies suggest a darker dimension, neuropsychiatric complications, which are a hallmark of neurovirulent viral pathogens. However, current evidence suggests that these complications, which may vary from mild to critical conditions such as meningitis and encephalitis, are not well understood, posing marked challenges in the realm of diagnosis and treatment. In other words, while neuropsychiatric presentations of DENV and MPXV appear as an area of concern, diagnosing these manifestations remains challenging owing to their general characteristics and overlap with those of other pathological conditions and the lack of the central nervous system (CNS)-focused diagnostic tools. This can delay early detection and subsequent appropriate surveillance of DENV- and MPXV-associated neuropsychiatric complications. The present review focuses on describing various DENV- and MPXV-associated neuropsychiatric complications, the underlying pathophysiological mechanisms, and their current diagnostic challenges.

Varicella zoster virus (VZV) causes herpes zoster ophthalmicus (HZO), a disease resulting from VZV reactivation in the eye branch of the trigeminal nerve, primarily affecting the elderly or immunocompromised. Current research on the relative prevalence of ocular HZO is limited to case series and reports. This study aims to conduct a systematic review and meta-analysis comparing the effects of antiviral drugs, corticosteroids, and their combination in published cases of ophthalmoplegic HZO. We reviewed the Scopus, PubMed, and Google Scholar databases for HZO-related studies, analysing all case reports and case series interventional studies. Our initial search yielded 14,100 articles, with 92 articles encompassing 111 patients included in the final analysis. Steroid treatment showed a greater improvement in visual score compared to antiviral treatment (ß = 0.80, 95% CI = 0.10, 1.50 = 1.10, p = 0.024). We found no significant relationship between treatment type and extraocular movement improvement (p > 0.05). While corticosteroid administration timing did not correlate with extraocular movement improvement (p = 0.108), increased acyclovir duration was associated with 3.64 times higher odds of improvement (OR = 3.64, 95% CI = 1.004, 13.23, p = 0.049). Patients with myositis had 19.42 times higher odds of skin involvement after orbital symptoms compared to those with orbital apex syndrome (OAS) (OR = 19.42, 95% CI = 1.16, 325.05, p = 0.039). Our findings suggest corticosteroid treatment may be more effective for visual outcomes than antiviral drugs or combination therapy. Additionally, longer antiviral therapy duration is linked to better extraocular motor outcomes. Most ophthalmoplegic HZO patients exhibited signs of aseptic meningitis in cerebrospinal fluid (CSF) examinations.

Arboviruses, including dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV), are vector-borne pathogens that exploit the mammalian target of rapamycin (mTOR) signalling pathway to optimise host cellular environments for replication, immune evasion, and pathogenesis. These viruses manipulate mTOR complexes through specific viral proteins, such as DENV NS5 activating mTORC2 to suppress apoptosis and ZIKV NS4A/NS4B inhibiting Akt-mTORC1 signalling to impair neurogenesis while promoting autophagy. JEV NS1/NS1' disrupts the blood-brain barrier by inducing autophagy-mediated degradation of tight junction proteins via mTOR suppression, contributing to encephalitis. These interactions result in severe pathological outcomes, including immune evasion, metabolic reprogramming, apoptosis suppression, and neurological disorders like microcephaly. Targeting mTOR has emerged as a promising therapeutic approach for arbovirus infections. Rapamycin and its derivatives reduce viral replication and improve survival in preclinical models, while repurposed drugs like niclosamide and chloroquine exhibit antiviral effects against ZIKV. ATP-competitive inhibitors such as Torin-1 and natural compounds like resveratrol expand the therapeutic landscape. Combination therapies pairing mTOR inhibitors with antivirals or immune modulators may provide synergistic benefits. This review highlights the molecular mechanisms underlying arbovirus manipulation of mTOR signalling and emphasises the potential of tailored therapeutic interventions targeting these pathways to mitigate arbovirus-associated diseases.

The Orf virus (ORFV) is the prototype member of the parapoxvirus family and has long been recognized for its robust immunogenicity, favourable safety profile and its ability to stimulate both cellular and humoural immune responses without inducing significant anti-vector immunity. Despite these inherent advantages, early applications of ORFV-based technologies were limited by challenges in manufacturing scalability and uncertainties regarding clinical safety in humans. However, recent breakthroughs have transformed this therapeutic landscape. A landmark achievement is the development of Prime-2-CoV, an ORFV-based anti-COVID-19 vaccine that has advanced into human clinical trials, providing the first clinical evidence of live ORFV's feasibility, safety and immunogenicity. This milestone, together with the establishment of a good manufacturing practice (GMP)-compliant production process and comprehensive preclinical evaluations, has laid a robust foundation for broader clinical applications of ORFV-based therapeutics. Moreover, the use of ORFV as an oncolytic virus therapy has shown promising results, effectively converting immunologically 'cold' tumours into 'hot' ones, underscoring its versatility as a therapeutic platform. In this review, we critically assess recent advances in ORFV-based therapeutics, with a particular focus on vaccine development and oncolytic virotherapy (OVT). We thoroughly discuss the milestones and impact of the first ORFV-based clinical trial, outline strategies for optimizing the technology and provide insights into overcoming remaining challenges. Collectively, these advancements position ORFV as a highly promising and versatile platform for next-generation prophylactic and therapeutic interventions in both human and veterinary medicine, while also providing a roadmap for future innovations.

COVID-19 has emerged as a global health crisis with significant consequences, not only for respiratory health but also for the cardiovascular system. This study aimed to investigate potential sex-based disparities in cardiovascular outcomes among individuals diagnosed with COVID-19 A systematic search was performed in PUBMED/MEDLINE, SCOPUS, and EMBASE, up until January 2024 to identify studies measuring the sex-based differences in cardiovascular outcomes associated with COVID-19. The outcomes of interest included (myocardial infarction, venous thromboembolism, ischemic stroke, major bleeding, mortality, heart failure and hospitalization length). The meta-analysis was performed using the 'Stata' software, version 18. We identified 11 studies involving 31,044 males and 25,917 females in our review. A slightly lower risk of myocardial infarction in females (RR: 1.24; 95% CI [1.03, 1.49]; p = 0.02) contrasted with a substantially increased risk of venous thromboembolic events (RR: 1.43; 95% CI [1.19, 1.71]; p = 0.00) in males. Additionally, males displayed a slightly higher risk of major bleeding (RR: 1.22; 95% CI [1.06, 1.40]; p = 0.00). This trend continued with significantly higher rates of extracorporeal membrane oxygenation (ECMO) utilization (RR: 2.14; 95% CI [1.11, 4.13]; p = 0.02) in males. Moreover, stroke outcomes and overall mortality were demonstrably worse for males (RR: 1.46; p = 0.05 and RR: 1.21; p = 0.00, respectively). Males with COVID-19 face higher risks of myocardial infarction, venous thromboembolism, ischemic stroke, major bleeding, and mortality. Heart failure and hospitalization length show no gender disparity. These findings highlight the crucial role of gender in COVID-19's cardiovascular complications.

Arboviruses are a group of arthropod-borne viral pathogens that pose a significant threat to the public health system. The clinical manifestations associated with these viruses range from self-limiting infections to life-threatening disorders. As a group of systemic viral infections, arboviruses can affect various parts of human organ systems, such as the nervous system. In the nervous system, epigenetic mechanisms are involved in various mechanisms including adult neurogenesis, neuronal-glial differentiation, the regulation of neural behaviour and neural plasticity, as well as other brain functions such as memory, and cognition. Hence, epigenetic deregulation is a key factor in the aetiology of different neurological disorders that highlights the importance of studying the underlying mechanisms and risk factors to introduce effective therapeutic approaches. There is mounting evidence that arboviruses that affect the nervous system take advantage of various mechanisms to modulate epigenetic processes to regulate their life cycles. This phenomenon may affect the nervous system leading to neurotropic arboviral infection-associated neurological disorders. Hence, it is important to understand reciprocal interplays between neurotropic arboviral pathogens and epigenetic processes to better control these disorders. The present review provides an overview of different interactions of arboviruses with epigenetic mechanisms during neurotropic arboviral infections. It uniquely focuses on the interplay between epigenetic modifications and arboviral neurotropism, shedding light on potential therapeutic strategies that have not been comprehensively addressed before. Targeting virus-induced epigenetic alterations, such as miRNA regulation, could lead to novel antiviral therapies aimed at mitigating neuroinflammation and disease severity.

West Nile virus (WNV), a globally distributed flavivirus, poses a significant public health threat, causing West Nile fever and potentially severe neuroinvasive disease in humans. The absence of specific antiviral treatments and licenced human vaccines underscores the importance of understanding WNV pathogenesis, particularly the mechanisms by which it evades host immune responses. This review comprehensively analyzes the multifaceted immune evasion strategies employed by WNV, encompassing the suppression of interferon (IFN) production and signalling through targeting of STAT proteins, IRF3, and RNA sensors, the modulation of antigen presentation via downregulation of MHC molecules and impairment of proteasome function, and the manipulation of cytokine and chemokine responses to dysregulate inflammation and promote viral persistence. Furthermore, WNV exploits the blood-brain barrier (BBB) to gain access to the central nervous system (CNS), both by disrupting the barrier integrity and utilising "Trojan horse" mechanisms. The potential for antibody-dependent enhancement (ADE) further complicates the host-virus interaction. Understanding these immune evasion mechanisms is crucial for deciphering WNV pathogenesis and informing the development of effective vaccines and targeted immunotherapies aimed at preventing and treating WNV-related diseases. Future research should focus on translating this knowledge into tangible clinical benefits for at-risk populations, particularly regarding strategies to induce broadly neutralising antibody responses and robust T-cell immunity while mitigating the risk of ADE.

Both health and economic burdens of dengue virus (DENV), as an increasingly prevalent pathogen and global threat, exist in endemic regions. Vaccination is a key strategy in decreasing dengue morbidity and mortality. This systematic review assesses the efficacy, immune response and safety of dengue vaccines (Qdenga (TAK-003) and Dengvaxia (CYD-TDV)) in adolescents against the need for evidence-based data for dengue vaccination strategies. We performed a systematic search of six databases (Scopus, PubMed, Web of Science, Cochrane, clinical trials. gov, and MEDLINE) for studies published until October 2024. A total of 482 articles were identified, 32 studies met the inclusion criteria after removing duplicates and title and abstract screening. Immunogenicity and safety profiles for both vaccines. TAK-003 showed high seropositivity rates with all of the four DENV serotypes, especially for DENV-2, with sustained antibody responses 3 years after vaccination. CYD-TDV induced neutralising antibodies with balanced activity, but such an immune response was most efficient in individuals with baseline seropositivity, for whom greater efficacy was observed. Most adverse events were mild to moderate, such as transitory pain at the injection site and headache, while serious adverse events were rare and did not correlate with vaccination. Nonetheless, specific issues regarding serotype-unique efficacy variations and the threat of vaccine-induced immune enhancement in seronegative groups contribute to worry. These findings highlighted the importance of TAK-003 and CYD-TDV in reducing the impact of dengue, especially in endemic regions. Ongoing research is essential to refine vaccine deployment strategies, optimise protection across diverse populations, and address outstanding concerns regarding long-term immunity and safety in seronegative individuals.

Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae, transmitted by a mosquito bite and is highly infectious in aerosol form. Inflammation plays a role of antiviral response as well as development of lethal encephalitis. Infection through a mosquito bite is biphasic, beginning with an inflammatory process and viral replication in different organs with subsequent infiltration to the central nervous system (CNS), inducing encephalitis. The direct route is through inhalation of aerosols containing the virus with direct brain infection through the olfactory nerve. Significant damage is due to exacerbated inflammation in the host. Angiotensin II (Ang II) is a molecule with high pro-inflammatory capacity, which has been found to be upregulated in the brain of VEEV-infected rats, suggesting its role in the pathogenesis of this disease. Limited information regarding the association of Ang II expression with VEEV brain infection has been reported. The aim of this review is to highlight published reports indicating a possible association between Ang II expression and VEEV-induced encephalitis. Several studies reflect a possible expression and function of Ang II during VEEV infection. Factors such as the relationship of Ang II with proteins involved in viral replication and entry into the cell (furin, Rab5, Rab7), activation of protein kinase C (necessary for the phosphorylation of VEEV), presence of microRNAs related to viral biology, increased permeability of the blood-brain barrier, and use of transcription pathways common to Ang II and VEEV, may conceivable an association of Ang II with the pathogenesis of VEEV encephalitis.