Primary Virus Research Articles

Seroprevalence of Rubella Virus Infection in Susceptible Women of Childbearing Age Group Seeking Preconceptional Counselling and Infertility Treatment- A Cross-sectional Study from Eastern India

Introduction: Rubella is an acute viral infection predominantly affecting children and adults. Although natural infection with rubella provide lifelong immunity, but, primary infection in pregnant women during the initial days of pregnancy may result in spontaneous abortion, stillbirth, or a baby born with Congenital Rubella Syndrome (CRS), which can be prevented by vaccinating the susceptible non immune females one month prior to planning conception. Aim: To determine rubella virus immune status and demographic profile of women in childbearing age group, and counsel all Rubella virus infection susceptible women for vaccination prior to planning pregnancy. Materials and Methods: A cross-sectional observational study was done at Indira Gandhi Institute of Medical Sciences (IGIMS), Patna , Bihar, India, on 112 apparently healthy, asymptomatic women in the 18-45 years age group coming for preconceptional counselling and primary and secondary infertility treatment during April 2017 to March 2019, whose serum rubella Immunoglobulin G (IgG) antibody testing was done by Enzyme- linked Immunosorbent Assay (ELISA). The data regarding their rubella virus immune status, age, parity and occupations were coded and recorded in MS Excel spreadsheet program. The Statistical Package for the Social Sciences (SPSS) version 23 (IBM Corp.) was used for data analysis. Results: Out of the total 112 women {92 (82.1%) housewife and 20 (17.9%) professionals} included in this study , a total of 67 (59.8%) women tested positive for rubella IgG antibody and 45 (40.2%) tested negative for rubella IgG antibody. The mean age of the rubella virus seropositive immune patients and seronegative susceptible women was 27.72±4.83 years was 26.09±4.68 years respectively. Among the 67 seropositive patients, maximum antirubella virus IgG seropositivity (71.4%) was seen in more than 35 years age group and maximum seronegativity 23 (46.9%) was seen in 18-26 years age group. There was no direct association of occupation and parity with rubella immune status. Conclusion: Higher rate of antirubella IgG seronegativity amongst younger age groups and nulliparous women renders them susceptible to primary Rubella virus infection. Hence, Rubella IgG antibody screening, proper counselling and prompt rubella vaccination for all primary Rubella virus infection susceptible women is necessary one month prior to planning conception, to avoid foetal congenital malformations during subsequent pregnancies.

Neurovirulence, viscerotropism and immunogenicity of live attenuated yellow fever 17D vaccine virus in non-human primates.

Yellow fever vaccine associated neurovirulence and viscerotropism have been reported by various countries. In this study, the neurovirulence, viscerotropism and immunogenicity of yellow fever vaccine seed lots (master and working) and final product manufactured at Serum Institute of India (SII) were evaluated in cynomolgus monkeys. WHO reference virus 168-73 and Stamaril™ as a control vaccine was used for comparison. Neurovirulence and viscerotropism scores of the seed lots and final product were lower than Stamaril™. The SII seed virus and vaccine complies to the WHO requirement for neurovirulence, viscerotropism and immunogenicity, when tested in comparison to WHO reference seed virus 168/73. All challenged animals showed 100% seroconversion as early as day 14 and neutralizing antibody titers were sustainable at day 30 in all animals.

Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.

Lopinavir and ritonavir (LPV/r) are the primary anti-human immunodeficiency virus (HIV) drugs recommended by the World Health Organization for treating children aged 3 years and above who are infected with the HIV. These drugs are typically available in liquid formulations to aid in dosing for children who cannot swallow tablets. However, the strong bitter taste associated with these medications can be a significant obstacle to adherence, particularly in young children, and can jeopardize the effectiveness of the treatment. Studies have shown that poor palatability can affect the survival rate of HIV-infected children. Therefore, developing more child-friendly protease inhibitor formulations, particularly those with improved taste, is critical for children with HIV. The molecular mechanism by which lopinavir and ritonavir activate bitter taste receptors, TAS2Rs, is not yet clear. In this study, we utilized a calcium mobilization assay to characterize the activation of bitter taste receptors by lopinavir and ritonavir. We discovered that lopinavir activates TAS2R1 and TAS2R13, while ritonavir activates TAS2R1, TAS2R8, TAS2R13, and TAS2R14. The development of bitter taste blockers that target these receptors with a safe profile would be highly desirable in eliminating the unpleasant bitter taste of these anti-HIV drugs.

A single-shot ChAd3-MARV vaccine confers rapid and durable protection against Marburg virus in nonhuman primates.

Marburg virus (MARV) causes a severe hemorrhagic fever disease in primates with mortality rates in humans of up to 90%. MARV has been identified as a category A bioterrorism agent by the Centers for Disease Control and Prevention (CDC) and priority pathogen A by the National Institute of Allergy and Infectious Diseases (NIAID), needing urgent research and development of countermeasures because of the high public health risk it poses. The recent cases of MARV in West Africa underscore the substantial outbreak potential of this virus. The potential for cross-border spread, as had occurred during the 2014-2016 Ebola virus outbreak, illustrates the critical need for MARV vaccines. To support regulatory approval of the chimpanzee adenovirus 3 (ChAd3)-MARV vaccine that has completed phase 1 trials, we showed that the nonreplicating ChAd3 vector, which has a demonstrated safety profile in humans, protected against a uniformly lethal challenge with MARV/Ang. Protective immunity was achieved within 7 days of vaccination and was maintained through 1 year after vaccination. Antigen-specific antibodies were an immune correlate of protection in the acute challenge model, and their concentration was predictive of protection. These results demonstrate that a single-shot ChAd3-MARV vaccine generated a protective immune response that was both rapid and durable with an immune correlate of protection that will support advanced clinical development.

Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates.

Small CD4-mimetic compound (CD4mc), which inhibits the interaction between gp120 with CD4, acts as an entry inhibitor and induces structural changes in the HIV-1 envelope glycoprotein trimer (Env) through its insertion within the Phe43 cavity of gp120. We recently developed YIR-821, a novel CD4mc, that has potent antiviral activity and lower toxicity than the prototype NBD-556. To assess the possibility of clinical application of YIR-821, we tested its antiviral activity using a panel of HIV-1 pseudoviruses from different subtypes. YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested and enhanced neutralization mediated by coreceptor binding site (CoRBS) antibodies in 50% (16/32) of these. Furthermore, when we assessed the antiviral effects using a panel of pseudoviruses and autologous plasma IgG, enhancement of antibody-mediated neutralization activity was observed for 48% (15/31) of subtype B strains and 51% (28/55) of non-B strains. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. Enhancement of antibody-dependent cellular cytotoxicity was also observed with YIR-821 for all six selected clinical isolates, as well as for the transmitted/founder (T/F) CH58 virus-infected cells. The sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821. Our findings may facilitate the clinical application of YIR-821. IMPORTANCE Small CD4-mimetic compound (CD4mc) interacts with the Phe43 cavity and triggers conformational changes, enhancing antibody-mediated neutralization and antibody-dependent cellular cytotoxicity (ADCC). Here, we evaluated the effect of YIR-821, a novel CD4mc, against clinical isolates, including both subtype B and non-B subtype viruses. Our results confirm the desirable properties of YIR-821, which include entry inhibition, enhancement of IgG-neutralization, binding, and ADCC, in addition to low toxicity and long half-life in a rhesus macaque model, that might facilitate the clinical application of this novel CD4mc. Our observation of primary viruses that are resistant to YIR-821 suggests that further development of CD4mcs with different structural properties is required.

Differences in Total S-RBD Antibody SARS-CoV-2 Post-vaccination mRNA-1273 3rd Dosage (Heterologous Prime Booster) with Post-prime Vaccination Inactivated Whole Virus Two Doses (Homologous) in Health Personnel Surabaya H2LC Clinic

SARS-CoV-2 cases have increased to 463,182,124 reported worldwide as of March 16, 2022 with a death toll of 6,079,600. Indonesia on March 17, 2022 has increased by 5,939,082 with a death toll of 153,212 (KPCPEN, 2022). SARS-CoV-2 is closely related to the coronavirus. One of the efforts made to prevent the risk of severe infection and reduce the death rate from the SARS-CoV-2 virus in Indonesia is a vaccination program. According to IDI (2021) cases of Covid-19 deaths are dominated by men (84%) and women (16%). Clinical trials in China and Brazil have shown that, the immunogenicity of two doses of the vaccine decreases over time and there is a decrease in low antibody concentrations after 6 months of running time. To overcome this potential, the Indonesian government gives priority to the 3rd vaccine booster. The purpose of this study was to analyze the comparison between the total antibody titer for the Spike-RBD (Receptor Binding Domain) SARS-CoV-2 protein after the 3rd dose of mRNA-1273 booster vaccination and post-vaccination of two doses of primary inactivated whole virus in health workers. This research was conducted by observation with a cohort approach. It was concluded that the results of the Mann Whitney two-sided test with a significance value of 0.000, the antibody titer correlation test results with gender had a value of 0.702 and -0.366 for the relationship between antibody titer and age. There was a significant difference between the primary vaccination dose of 2 doses of CoronaVac and the 3rd vaccination (booster) mRNA-1273, gender was strongly associated with S-RBD antibody titer and age was not associated with S-RBD antibody titer.

Differences in Total S-RBD Antibody SARS-CoV-2 Post-vaccination mRNA-1273 3rd Dosage (Heterologous Prime Booster) with Post-prime Vaccination Inactivated Whole Virus Two Doses (Homologous) in Health Personnel Surabaya H2LC Clinic

SARS-CoV-2 cases have increased to 463,182,124 reported worldwide as of March 16, 2022 with a death toll of 6,079,600. Indonesia on March 17, 2022 has increased by 5,939,082 with a death toll of 153,212 (KPCPEN, 2022). SARS-CoV-2 is closely related to the coronavirus. One of the efforts made to prevent the risk of severe infection and reduce the death rate from the SARS-CoV-2 virus in Indonesia is a vaccination program. According to IDI (2021) cases of Covid-19 deaths are dominated by men (84%) and women (16%). Clinical trials in China and Brazil have shown that, the immunogenicity of two doses of the vaccine decreases over time and there is a decrease in low antibody concentrations after 6 months of running time. To overcome this potential, the Indonesian government gives priority to the 3rd vaccine booster. The purpose of this study was to analyze the comparison between the total antibody titer for the Spike-RBD (Receptor Binding Domain) SARS-CoV-2 protein after the 3rd dose of mRNA-1273 booster vaccination and post-vaccination of two doses of primary inactivated whole virus in health workers. This research was conducted by observation with a cohort approach. It was concluded that the results of the Mann Whitney two-sided test with a significance value of 0.000, the antibody titer correlation test results with gender had a value of 0.702 and -0.366 for the relationship between antibody titer and age. There was a significant difference between the primary vaccination dose of 2 doses of CoronaVac and the 3rd vaccination (booster) mRNA-1273, gender was strongly associated with S-RBD antibody titer and age was not associated with S-RBD antibody titer.

DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test

BackgroundCervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients.ResultsThe WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case–control) and predictive setting (nested case–control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt−) index sample who were diagnosed with CIN3 1–4 years after sample donation.ConclusionWe identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case–control settings and future studies will assess performance and generalisability in a randomised controlled trial.

Rotavirus vaccine clinical trials: a cross-sectional analysis of clinical trials registries

BackgroundRotavirus is a primary infectious virus causing childhood diarrhoea and is associated with significant mortality in children. Three African countries (Nigeria, the Democratic Republic of Congo, and Angola) are among the five countries that account for 50% of all diarrheal-related deaths worldwide. This indicates that much needs to be done to reduce this burden. The World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) is a global repository for primary registries reporting on clinical trials. This study aimed to identify and describe planned, ongoing, and completed rotavirus vaccine trials conducted globally.MethodsWe searched WHO-ICTRP on 17 June 2021 and conducted a cross-sectional analysis of rotavirus studies listed in the database. Data extraction included trial location, participant age, source of the trial record, trial phase, sponsor, and availability of results. We used the Microsoft Excel 365 package to generate descriptive summary statistics.ResultsWe identified 242 rotavirus vaccine trials registered from 2004 to 2020. Most of these trials were registered retrospectively, with only 26% of the rotavirus vaccine trials reporting the availability of results in their registries. Most of the trials are studying children aged less than 5 years. The recruitment status for these trials is currently shown in the WHO-ICTRP as “not recruiting” for 80.17% of trials, “recruiting” for 11.57% of trials recruiting, and unknown for 6.61% of trials. The continents in which these rotavirus vaccine trials have recruitment sites in Asia (41%) and North America (20%), with the maximum number of trials in the clinical trial registries coming from India (21%) and the USA (11%) with most being sponsored by the pharmaceutical industry. Our analysis shows that only 26% of the rotavirus vaccine trials report the availability of results in their registries.ConclusionsMapping rotavirus vaccine clinical trial activity using data from the WHO ICTRP beneficial provides valuable information on planned, ongoing, or completed trials for researchers, funders, and healthcare decision-makers. Despite the high rotavirus disease burden in low- and middle-income countries, including Africa, there is minimal clinical trial activity related to the condition on the continent. The clinical trial registries as a valuable tool to share interim results of the trials.

Seroprevalence of Chikungunya and Zika virus in nonhuman primates: A systematic review and meta-analysis

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are mosquito-borne viruses that have caused several outbreaks worldwide. Aedes mosquitoes transmit these viruses mainly through sylvatic and urban transmission cycles. In the sylvatic cycle, nonhuman primates (NHPs) can be infected with CHIKV and ZIKV and may play an essential role as reservoirs for virus transmission. To improve our knowledge on the role of NHPs in the sylvatic cycle, we performed a systematic review and meta-analysis study on the seroprevalence of CHIKV and ZIKV worldwide in NHPs. According to the PRISMA guidelines, 17 CHIKV and 16 ZIKV seroprevalence studies in NHPs from 3 online databases: PubMed, Embase, and Scopus were selected. Data were extracted, including location and study year, type of NHP, sample size, serological tests, and seropositivity. All included studies have high-quality scores, between 5 and 8, corresponding to the grading criteria. Seroprevalence estimation was pooled using the ‘meta’ package in the R statistical software. The estimated pooled seroprevalence of CHIKV and ZIKV in NHP was 17% (95%CI: 5–34, I2: 99%, p < 0.05) and 6% (95% CI: 2–12, I2: 92%, p < 0.05), respectively. Most of the NHPs tested were wild Old World monkeys. The subgroup was analyzed by continents; high seropositive CHIKV and ZIKV were found in African NHPs at 35% (95% CI 9–66.0, I2 = 100) and 16% (95% CI 1–44, I2 = 97), respectively. While NHPs in America have 7% (95% CI 0-28, I2 = 99) and 2% (95% CI 1-3, I2 = 54) against CHIKV and ZIKV. In Asia, 6% (95% CI: 5–34, I2 = 96) CHIKV seroprevalence and 7% (95% CI 0–20, I2 = 98) ZIKV seroprevalence were found in NHP. This study provides a comprehensive overview of the seroprevalence of CHIKV and ZIKV among NHPs in various regions.

The Ability of Postimmunobiotics from L. rhamnosus CRL1505 to Protect against Respiratory Syncytial Virus and Pneumococcal Super-Infection Is a Strain-Dependent Characteristic.

Previously, we demonstrated that the non-viable strain Lacticaseibacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulated the respiratory innate antiviral immune response triggered by Toll-like receptor (TLR)-3 activation in infant mice, improving the resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In this work, we evaluated the effect of other non-viable L. rhamnosus strains and their peptidoglycans on the respiratory immune response and their impact on primary and secondary respiratory infections. In addition, the duration of the protective effect induced by NV1505 and PG1505 as well as their ability to protect against different Streptococcus pneumoniae serotypes were evaluated. Our results showed that among the five selected L. rhamnosus strains (CRL1505, CRL498, CRL576, UCO25A and IBL027), NV1505 and NVIBL027 improved the protection against viral and pneumococcal infections by modulating the respiratory immune response. Of note, only the PG1505 presented immunomodulatory activities when compared with the other purified peptidoglycans. Studies on alveolar macrophages showed that NV1505 and PG1505 differentially modulated the expression of IL-6, IFN-γ, IFN-β, TNF-α, OAS1, RNAseL and IL-27 genes in response to RSV infection, and IL-6, IFN-γ, IL-1β, TNF-α, CCL2, CXCL2, CXCL10 and IL-27 in response to pneumococcal challenge. Furthermore, we demonstrated that NV1505 and PG1505 treatments protected mice against secondary pneumococcal pneumonia produced by different serotypes of S. pneumoniae until 30 days after stimulation with poly(I:C). This work advances the characterization of the protective effect of NV1505 and PG1505 by demonstrating that they increase resistance against the pneumococcal serotypes 3, 6B, 14 and 19F, with an effect that lasts up to 30 days after the primary viral inflammation. The results also confirm that the immunomodulatory properties of NV1505 and PG1505 are unique and are not shared by other members of this species, and suggest the existence of a capacity to stimulate trained immunity in alveolar macrophages.

Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies.

Several studies have shown that the first encounter with influenza virus shapes the immune response to future infections or vaccinations. However, a detailed analysis of the primary antibody response is lacking as this is difficult to study in humans. It is therefore not known what the frequency and dynamics of the strain-specific hemagglutinin (HA) head- and stem-directed antibody responses are directly after primary influenza virus infection. Here, sera of twelve H1N1pdm2009 influenza virus-infected cynomolgus macaques were evaluated for HA-head and HA-stem domain antibody responses. We observed an early induction of HA-stem antibody responses, which was already decreased by day 56. In contrast, responses against the HA-head domain were low early after infection and increased at later timepoint. The HA-specific B cell repertoires in each animal showed diverse VH-gene usage with preferred VH-gene and JH-gene family usage for HA-head or HA-stem B cells but a highly diverse allelic variation within the VH-usage. HA-head B cells had shorter CDRH3s and higher VH-gene somatic hyper mutation levels relative to HA-stem B cells. In conclusion, our data suggest that HA-stem antibodies are the first to react to the infection while HA-head antibodies show a delayed response, but a greater propensity to enter the germinal center and undergo affinity maturation.

Blocking Autophagy in M1 Macrophages Enhances Virus Replication and Eye Disease in Ocularly Infected Transgenic Mice.

Macrophages are one of the first innate immune infiltrates in the cornea of mice following ocular infection with herpes simplex virus 1 (HSV-1). Using gamma interferon (IFN-γ) and interleukin-4 (IL-4) injections to polarize macrophages into M1 and M2, respectively, and in M1 and M2 conditional knockout mice, we have shown that M1 macrophages play an important role in suppressing both virus replication in the eye and eye disease in HSV-1-infected mice. Autophagy is also important in controlling HSV infection and integrity of infected cells. To determine if blocking autophagy in M1 and M2 macrophages affects HSV-1 infectivity and eye disease, we generated two transgenic mouse strains expressing the HSV-1 γ34.5 autophagy gene under the M1 promoter (M1-γ34.5) or the M2 promoter (M2-γ34.5). We found that blocking autophagy in M1 macrophages increased both virus replication in the eyes and eye disease in comparison to blocking autophagy in M2 macrophages or wild-type (WT) control mice, but blocked autophagy did not affect latency-reactivation. However, blocking autophagy affected fertility in both M1 and M2 transgenic mice. Analysis of 62 autophagy genes and 32 cytokines/chemokines from infected bone marrow-derived macrophages from M1-γ34.5, M2-γ34.5, and WT mice suggested that upregulation of autophagy-blocking genes (i.e., Hif1a, Mtmr14, mTOR, Mtmr3, Stk11, and ULK2) and the inflammatory tumor necrosis factor alpha (TNF-α) gene in M1-γ34.5 transgenic mice correlated with increased pathogenicity, while upregulation of proautophagy genes (Nrbf2 and Rb1cc1) in M2-γ34.5 macrophages correlated with reduced pathogenicity. The in vivo and in vitro responses of M1-γ34.5 and M2-γ34.5 transgenic mice to HSV-1 infection were independent of the presence of the γ34.5 gene in wild-type HSV-1. Our results suggest that M1 macrophages, but not M2 macrophages, play an important role in autophagy relative to primary virus replication in the eye and eye disease in infected mice. IMPORTANCE Autophagy plays a critical role in clearing, disassembling, and recycling damaged cells, thus limiting inflammation. The HSV-1 γ34.5 gene is involved in neurovirulence and immune evasion by blocking autophagy in infected cells. We found that blocking autophagy in M1 macrophages enhances HSV-1 virus replication in the eye and eye disease in ocularly infected transgenic mice. Our results also show the suppressive effects of γ34.5 on immune responses to infection, suggesting the importance of intact autophagy in M1 but not M2 macrophages in controlling primary infection and eye disease.

Simultaneous Detection of SARS-CoV-2 and Influenza Virus in Wastewater of Two Cities in Southeastern Germany, January to May 2022.

Dependent on the excretion pattern, wastewater monitoring of viruses can be a valuable approach to characterizing their circulation in the human population. Using polyethylene glycol precipitation and reverse transcription-quantitative PCR, the occurrence of RNA of SARS-CoV-2 and influenza viruses A/B in the raw wastewater of two treatment plants in Germany between January and May 2022 was investigated. Due to the relatively high incidence in both exposal areas (plant 1 and plant 2), SARS-CoV-2-specific RNA was determined in all 273 composite samples analyzed (concentration of E gene: 1.3 × 104 to 3.2 × 106 gc/L). Despite a nation-wide low number of confirmed infections, influenza virus A was demonstrated in 5.2% (concentration: 9.8 × 102 to 8.4 × 104 gc/L; plant 1) and in 41.6% (3.6 × 103 to 3.0 × 105 gc/L; plant 2) of samples. Influenza virus B was detected in 36.0% (7.2 × 102 to 8.5 × 106 gc/L; plant 1) and 57.7% (9.6 × 103 to 2.1 × 107 gc/L; plant 2) of wastewater samples. The results of the study demonstrate the frequent detection of two primary respiratory viruses in wastewater and offer the possibility to track the epidemiology of influenza by wastewater-based monitoring.

Knockout of signal peptide peptidase in the eye reduces HSV-1 replication and eye disease in ocularly infected mice.

We previously reported that knocking out signal peptide peptidase (SPP), a glycoprotein K (gK) binding partner, in mouse peripheral sensory neurons reduced latency-reactivation in infected mice without affecting primary virus replication or eye disease. Since virus replication in the eye plays an essential role in eye disease, we generated a conditional knockout mouse lacking SPP expression in the eye by crossing Pax6 (paired box 6)-Cre mice that have intact Pax6 expression with SPPflox/flox mice. Significantly less SPP protein expression was detected in the eyes of Pax6-SPP-/- mice than in WT control mice. HSV-1 replication in the eyes of Pax6-SPP-/- mice was significantly lower than in WT control mice. Levels of gB, gK, and ICP0 transcripts in corneas, but not trigeminal ganglia (TG), of Pax6-SPP-/- infected mice were also significantly lower than in WT mice. Corneal scarring and angiogenesis were significantly lower in Pax6-SPP-/- mice than in WT control mice, while corneal sensitivity was significantly higher in Pax6-SPP-/- mice compared with WT control mice. During acute viral infection, absence of SPP in the eye did not affect CD4 expression but did affect CD8α and IFNγ expression in the eye. However, in the absence of SPP, latency-reactivation was similar in Pax6-SPP-/- and WT control groups. Overall, our results showed that deleting SPP expression in the eyes reduced primary virus replication in the eyes, reduced CD8α and IFNγ mRNA expression, reduced eye disease and reduced angiogenesis but did not alter corneal sensitivity or latency reactivation to HSV-1 infection. Thus, blocking gK binding to SPP in the eye may have therapeutic potential by reducing both virus replication in the eye and eye disease associated with virus replication.

Age-specific hospitalization risk of primary and secondary respiratory syncytial virus infection among young children

ObjectivesElucidating the infection dynamics that lead to severe respiratory syncytial virus (RSV) pneumonia and hospitalization among young children are critical. We explored the role of infection parity as well as age in months for RSV-associated hospitalization among young children in Japan. MethodsWe used a sequential transmission catalytic model to capture the transmission mechanisms of RSV among infants in an endemic state. We investigated data on the age-dependent seroprevalence and incidence rate of hospitalization in Japan, and jointly estimated the age-specific risk of hospitalization during primary RSV infection and relative risk of hospitalization during secondary infection in children aged <5 years. ResultsThe estimated risk of hospitalization with primary infection was 0.08 (95% CI: 0.05-0.14) in infants aged 0-2 months. The estimated relative risk of hospitalization owing to secondary infection was 0.18 (95% CI: 0.01-2.04). ConclusionOur simple models successfully captured the infection dynamics of RSV among young children in Japan. The age group of early infancy may be most vulnerable to infection and hospitalization, offering key insights into future vaccinations. The burden of hospitalization from secondary infection may be less important in young children.

Discovery of two novel Torque Teno viruses in Callithrix penicillata provides insights on Anelloviridae diversification dynamics.

The development of high-throughput sequencing (HTS) technologies and metagenomics protocols deeply impacted the discovery of viral diversity. Moreover, the characterization of novel viruses in the Neotropical primates (NP) is central for the comprehension of viral evolution dynamics in those hosts, due to their evolutionary proximity to Old World primates, including humans. In the present work, novel anelloviruses were detected and characterized through HTS protocols in the NP Callithrix penicillata, the common black-tufted marmoset. De novo assembly of generated sequences was carried out, and a total of 15 contigs were identified with complete Anelloviridae ORF1 gene, two of them including a flanking GC-rich region, confirming the presence of two whole novel genomes of ~3 kb. The identified viruses were monophyletic within the Epsilontorquevirus genus, a lineage harboring previously reported anelloviruses infecting hosts from the Cebidae family. The genetic divergence found in the new viruses characterized two novel species, named Epsilontorquevirus callithrichensis I and II. The phylogenetic pattern inferred for the Epsilontorquevirus genus was consistent with the topology of their host species tree, echoing a virus-host diversification model observed in other viral groups. This study expands the host span of Anelloviridae and provides insights into their diversification dynamics, highlighting the importance of sampling animal viral genomes to obtain a clearer depiction of their long-term evolutionary processes.

Monkeypox: The Re-emerging Terror.

Monkeypox is a zoonotic Orthopoxvirus called human Monkeypox. It has symptoms that resemble or are pretty similar to smallpox. Monkeypox virus belongs to the genus Orthopoxvirus, which also includes cowpox, vaccinia, and variola viruses. The World Health Organization confirmed in 1970 that the primary virus is the Orthopoxvirus infecting humans after smallpox elimination. Clinically distinguishing the condition from varicella and smallpox is challenging for a clinician. Although the mortality rate of this disease is low, new tests are being tried and studied, which are required for a more accurate and quick diagnosis because the lab diagnosis is the key to the detection of illness and its monitoring. The illness or the virus is endemic to parts of western and central Africa. Surveillance in underdeveloped rural regions is challenging but manageable with evidence-based techniques and training materials for public health professionals. However, as in the present scenario, the disease is having a worldwide outbreak in various countries, and recently India detected its first case on 15 July 2022 in New Delhi. The widespread disease is due to trading exotic pets and international travel. Since smallpox vaccinations are not administered to people regularly, epidemiological studies are required. New medications and vaccines provide hope for treating and preventing Monkeypox; however, further study is required before they can be used effectively. Also, there is a requirement for advanced scientific studies in the etiology, epidemiology, and biological structure of the virus in the endemic zones to know and halt the spread of infection to humans.

Antiviral efficacy of favipiravir against Zika and SARS-CoV-2 viruses in non-human primates

The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising in vitro results to successful clinical implementation. Among the drugs that have been largely tested in clinical trials but failed so far to bring clear evidence of clinical efficacy is favipiravir, a nucleoside analogue with large spectrum activity against several RNA viruses in vitro and in small animal models. Here, we evaluate the antiviral activity of favipiravir against Zika or SARS-CoV-2 virus in cynomolgus macaques. In both models, high doses of favipiravir are initiated before infection and viral kinetics are evaluated during 7 to 15 days after infection. Favipiravir leads to a statistically significant reduction in plasma Zika viral load compared to untreated animals. However, favipiravir has no effects on SARS-CoV-2 viral kinetics, and 4 treated animals have to be euthanized due to rapid clinical deterioration, suggesting a potential role of favipiravir in disease worsening in SARS-CoV-2 infected animals. To summarize, favipiravir has an antiviral activity against Zika virus but not against SARS-CoV-2 infection in the cynomolgus macaque model. Our results support the clinical evaluation of favipiravir against Zika virus but they advocate against its use against SARS-CoV-2 infection.

Differential proteome response to H5N1 highly pathogenic avian influenza (HPAI) viruses infection in duck.

Ducks and wild aquatic birds are the natural reservoirs of avian influenza viruses. However, the host proteome response that causes disease in vivo by the H5N1 HPAI virus is still unclear. This study presented a comprehensive analysis of the proteome response in Muscovy duck lung tissue during 3 days of infection with either a highly virulent DK383 or an avirulent DK212. An unbiased strategy- isobaric tags for relative and absolute quantitation (iTRAQ) in conjunction with high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was utilized to investigate the infection mechanism. Pathways derived from analysis of 292 significantly altered proteins may contribute to the high pathogenic nature and disease progression of H5N1 viruses. Global proteome profiles indicated improved correlation with the virus titers and gene expression patterns between the two strains of the H5N1 virus. DK383 replicated more efficiently and induced a stronger response specific to severe disease. While proteins involved in the immune response of neutrophils were increased markedly by DK383, DK212 evoked a distinct response characterized by an increase in proteins involved in the maturation of dendritic cells, adhesion of phagocytes, and immune response of macrophages. The differentially activated Akt/mTOR/p70S6K pathway might involve in the host response to H5N1 viruses. Therefore, systematically integrated with datasets from primary genomic and virus titer results, proteomic analyses may help reveal the potential pathogenesis.