A Novel Recognition by the E3 Ubiquitin Ligase of HSV-1 ICP0 Enhances the Degradation of PML Isoform I to Prevent ND10 Reformation in Late Infection.

Upon viral entry, components of ND10 nuclear bodies converge with incoming DNA to repress viral expression. The infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) contains a RING-type E3 ubiquitin ligase that targets the ND10 organizer, PML, for proteasomal degradation. Consequently, ND10 components are dispersed and viral genes are activated. Previously, we reported that ICP0 E3 differentiates two similar substrates, PML isoforms I and II, and demonstrated that SUMO-interaction has profound regulatory effects on PML II degradation. In the present study, we investigated elements that regulate the PML I degradation and found that: (i) two regions of ICP0 flanking the RING redundantly facilitate the degradation of PML I; (ii) downstream of the RING, the SUMO-interaction motif located at residues 362-364 (SIM362-364) targets the SUMOylated PML I in the same manner as that of PML II; (iii) upstream of the RING, the N-terminal residues 1-83 mediate PML I degradation regardless of its SUMOylation status or subcellular localization; (iv) the reposition of residues 1-83 to downstream of the RING does not affect its function in PML I degradation; and (v) the deletion of 1-83 allows the resurgence of PML I and reformation of ND10-like structures late in HSV-1 infection. Taken together, we identified a novel substrate recognition specific for PML I, by which ICP0 E3 enforces a continuous PML I degradation throughout the infection to prevent the ND10 reformation.

The Role of ND10 Nuclear Bodies in Herpesvirus Infection: A Frenemy for the Virus?

Nuclear domains 10 (ND10), a.k.a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses. The diversity and dynamics of ND10 residents enable them to play seemingly opposite roles under different physiological conditions. Although the molecular mechanisms are not completely clear, the pro- and anti-cancer effects of ND10 have been well established in tumorigenesis. However, in herpesvirus research, until the recently emerged evidence of pro-viral contributions, ND10 nuclear bodies have been generally recognized as part of the intrinsic antiviral defenses that converge to the incoming viral DNA to inhibit the viral gene expression. In this review, we evaluate the newly discovered pro-infection influences of ND10 in various human herpesviruses and analyze their molecular foundation along with the traditional antiviral functions of ND10. We hope to shed light on the explicit role of ND10 in both the lytic and latent cycles of herpesvirus infection, which is imperative to the delineation of herpes pathogenesis and the development of prophylactic/therapeutic treatments for herpetic diseases.

Towards Improved Use of Vaccination in the Control of Infectious Bronchitis and Newcastle Disease in Poultry: Understanding the Immunological Mechanisms.

Infectious bronchitis (IB) and Newcastle disease (ND) are two important diseases of poultry and have remained a threat to the development of the poultry industry in many parts of the world. The immunology of avian has been well studied and numerous vaccines have been developed against the two viruses. Most of these vaccines are either inactivated vaccines or live attenuated vaccines. Inactivated vaccines induce weak cellular immune responses and require priming with live or other types of vaccines. Advanced technology has been used to produce several types of vaccines that can initiate prime immune responses. However, as a result of rapid genetic variations, the control of these two viral infections through vaccination has remained a challenge. Using various strategies such as combination of live attenuated and inactivated vaccines, development of IB/ND vaccines, use of DNA vaccines and transgenic plant vaccines, the problem is being surmounted. It is hoped that with increasing understanding of the immunological mechanisms in birds that are used in fighting these viruses, a more successful control of the diseases will be achieved. This will go a long way in contributing to global food security and the economic development of many developing countries, given the role of poultry in the attainment of these goals.

Coinfection of Tuberculosis and HIV in Nigeria: A Systematic Review and Meta-analysis.

Tuberculosis (TB) and HIV/AIDS are major public health issues globally. The burden of these diseases is particularly significant in Nigeria due to the high TB and HIV/AIDS prevalence. This meta-analysis for the 1st time addressed the TB/HIV coinfection prevalence in Nigeria at the regional level. A total of 58 relevant publications comprising 80 studies (n = 44,508) were obtained from PUBMED, ScienceDirect, African Journals Online, and Cochrane Library databases using carefully constructed keywords combinations. The PRISMA guideline was followed for this meta-analysis. Two independent reviewers conducted the publication screening, data extraction and methodological quality appraisal with a third reviewer serving as arbitrator. The pooled estimates were calculated using the random effects model. Heterogeneity was assessed using Cochran's Q and I 2 statistic. Univariate and multivariate meta-regressions were done to predict sources of between-study heterogeneity. Overall, the pooled prevalence of TB/HIV coinfection was 25.8%. The highest coinfection prevalence of 34.3% was recorded among the North Central States of Nigeria, while the least prevalence of 19.3% was recorded among the Southeastern states of Nigeria. There was a paucity of published articles from the Northeastern states of Nigeria. There was a significant heterogeneity between studies (I2 > 90%, p < 0.001), but meta-regression analysis only explained < 10% of it. This study has shown that the prevalence of TB/HIV coinfection remains significantly high in Nigeria. Constant surveillance should be rigorously implemented with special attention given to the Northeast due to the ongoing crises that are compounding the problem.

Immune Response to Herpes Simplex Virus Infection and Vaccine Development.

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

Seroprevalence of herpes simplex virus types 1 and 2 in Nigeria: a systematic review and meta-analyses.

A source of comprehensive information on the prevalence of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) can help researchers and policymakers address HSV related burden in the society. At the moment, this is not readily available. This study aims to fill this gap by attempting to estimate the seroprevalence of HSV-1 and HSV-2 infections in Nigeria on the basis of published data. A systematic review and meta-analysis including cross-sectional studies on HSV-1 and HSV-2 in Nigeria was conducted. Electronic databases including PubMed/MEDLINE, CENTRAL, African Journals Online (AJOL), ScienceDirect, WHO-Afro Library, WHO-IRIS and African Index Medicus were searched for English Language publications on HSV-1 and HSV-2. Seven relevant publications were identified. Seroprevalence measures of 3 and 23 for HSV-1 and HSV-2, respectively, were extracted. The pooled mean seroprevalences for HSV-1 and HSV-2 were 74.0% (37.4-99.4%) and 63.4% (56.1-70.4%) respectively. The mean seroprevalence of HSV-1 was higher among females, 82.4% (n = 509, CI, 36.6-100.0%), than males, 54.5% (n = 198, CI, 47.6-61.4%). The mean seroprevalence of HSV-2 were 51.8% (n = 1414, CI: 39.4-64.0%) and 86.5% (n = 162, CI: 80.8-91.3%) among healthy and clinical populations, respectively. The study was limited by the paucity of quality studies, variations in diagnostic methods and high heterogeneity in seroprevalence estimates. In conclusion, the seroprevalence of HSV-1 and HSV-2 remain high in Nigeria. Large and representative national epidemiological surveys covering all regions and specific groups are recommended.