Herpes Simplex Virus: A Versatile Tool for Insights Into Evolution, Gene Delivery, and Tumor Immunotherapy

Herpesviruses are prevalent throughout the animal kingdom, and they have coexisted and coevolved along with their host species for millions of years. Herpesviruses carry a large (120-230 kb) double-stranded DNA genome surrounded by a protein capsid, a tegument layer consisting of viral and host proteins, and a lipid bilayer envelope with surface glycoproteins. A key characteristic of these viruses is their ability to enter a latent state following primary infection, allowing them to evade the host’s immune system and persist permanently. Herpesviruses can reactivate from their dormant state, usually during times of stress or when the host’s immune responses are impaired. While herpesviruses can cause complications with severe disease in immune-compromised people, most of the population experiences few ill effects from herpesvirus infections. Indeed, herpes simplex virus 1 (HSV-1) in particular has several features that make it an attractive tool for therapeutic gene delivery. Herpes simplex virus 1 targets and infects specific cell types, such as epithelial cells and neurons. The HSV-1 genome can also accommodate large insertions of up to 14 kb. The HSV-1-based vectors have already achieved success for the oncolytic treatment of melanoma. In addition to serving as a vehicle for therapeutic gene delivery and targeted cell lysis, comparative genomics of herpesviruses HSV-1 and 2 has revealed valuable information about the evolutionary history of both viruses and their hosts. This review focuses on the adaptability of HSV-1 as an instrument for gene delivery and an evolutionary marker. Overall, HSV-1 shows great promise as a tool for treating human disease and studying human migration patterns, disease outbreaks, and evolution.

Effect of Hepatitis B Virus (HBV) Infection on Lipid Profile in Ghanaian Patients

Background: Worldwide, approximately 257 million people have chronic hepatitis B virus (HBV) infection, with the highest infection rates recorded in Africa and Asia. Although HBV infection has been associated with dyslipidemia, which may lead to death via liver related complications, the effect of the virus on the lipid profile of patients remain unclear. This study was designed to evaluate the effect of chronic hepatitis B virus infection on lipid profile of sero-positive individuals from Ghana. Methods: Blood samples were collected from chronic HBV infected patients who were recruited from the Korle-Bu Teaching Hospital, Accra, and HBV sero-negative healthy volunteers who were used as controls. Demographic and clinical data were obtained using a structured questionnaire. Blood pressure and body mass index were determined, and HBV profile markers and lipid profiles of the patients were determined using a commercially available kit and a chemistry analyzer, respectively. Results: Triglycerides, low density lipoproteins (LDL), high density lipoproteins (HDL), very low density lipoproteins (VLDL), and total cholesterol were used as indices of lipid metabolism disorder. Body mass index and diastolic blood pressures were significantly elevated in patients compared to healthy volunteers. Conclusion: The observed high total cholesterol and LDL, with a significantly lower HDL levels compared to healthy controls suggest an increased cardiovascular disease risk index in the patients. There is therefore the need to regularly monitor HBV infected patients for signs of cardiovascular diseases.

Very Early Cytomegalovirus Infection After Renal Transplantation: A Single-Center 20-Year Perspective

Background: Cytomegalovirus (CMV) infection risk in the first month after transplantation is felt to be minimal; however, the epidemiology has not been specifically investigated, particularly in the modern era of potent immunosuppressive regimens and universal CMV prophylaxis. Objective: The aim of this study was to describe the incidence of and risk factors associated with CMV occurring less than 30 days after transplant and evaluate the effect of very early CMV on outcomes. Methods: Retrospective, single-center study of adult renal transplant (RTX) recipients between January 1, 1994 and December 31, 2014. Results: A total of 5225 patients who received a renal transplant in the study time period were reviewed for the presence of CMV infection occurring less than 30 days after transplant. Of these, only 14 patients demonstrated this finding for an overall incidence of 0.27%. Half of these patients were considered to be at heightened risk due to being a recipient of a non-primary transplant or on chronic immunosuppression. This left seven patients without known risk factors for very early CMV to evaluate. In this group, time from transplant to CMV infection was 13.5 ± 7 days. The majority (57.1%, n = 4) were high-risk serostatus (CMV D+/R−) and occurred in the valganciclovir era (71.4%, n = 5). Lymphocyte-depleting induction predominated (57.1%, n = 4). Average cold ischemic time (CIT) was 19.7 ± 7.7 hours. Three patients had post-operative complications, two required exploratory-laparotomy for hemorrhage. When evaluating outcomes, 43% (n = 3) had subsequent episodes of CMV infection, 28.6% (n = 2) developed rejection, and 28.6% (n = 2) died. Outcomes between patients with CMV infection less than 30 days and those with CMV infection more than 30 days after transplant were not significantly different. Conclusions: In our review of over 5000 kidney transplants, the incidence of CMV infection in the first 30 days after renal transplant is 0.2%. Notable common patient characteristics include hemorrhage requiring re-operation and prolonged CIT. Outcomes were similar to CMV occurring more than 30 days after transplant. This study should provide the clinician with some reassurance; despite potent immunosuppressive therapy, CMV infection in the first 30 days is unlikely.

Filovirus Disease Outbreaks: A Chronological Overview

Filoviruses cause outbreaks which lead to high fatality in humans and non-human primates, thus tagging them as major threats to public health and species conservation. In this review, we give account of index cases responsible for filovirus disease outbreaks that have occurred over the past 52 years in a chronological fashion, by describing the circumstances that led to the outbreaks, and how each of the outbreaks broke out. Since the discovery of Marburg virus and Ebola virus in 1967 and 1976, respectively, more than 40 filovirus disease outbreaks have been reported; majority of which have occurred in Africa. The chronological presentation of this review is to provide a concise overview of filovirus disease outbreaks since the discovery of the viruses, and highlight the patterns in the occurrence of the outbreaks. This review will help researchers to better appreciate the need for surveillance, especially in areas where there have been no filovirus disease outbreaks. We conclude by summarizing some recommendations that have been proposed by health and policy decision makers over the years.

Seroprevalence and Associated Risk Factors of Hepatitis B Virus Infection Among Children in Enugu Metropolis

Background: Though measures are being put in place for the management of Hepatitis B virus (HBV) infection in Nigeria, children remain the most vulnerable to develop chronic hepatitis. Routine screening in children is therefore necessary for effective control. However, the performance of the commonly used immunochromatographic test (ICT) strips has been challenging. Also, identifying the risk factors of transmission in this age group is of importance for the implementation of preventive measures. Hence, the goal of this study was to assess the test performance of the routinely used ICT strip and identify the associated clinical manifestations and risk factors of HBV. Methods: A cross sectional study involving 270 children below six years of age was conducted at ESUTH and Favor Child Pediatrics Hospital in Enugu, Nigeria. The subjects were screened for HBV by ICT and ELISA assays and a structured questionnaire was used to obtain participants data including demographic, socioeconomic, signs and symptoms, risk factors and vaccination. Results: BBased on ELISA, 31 out of 270 children were positive for HBV with an infection rate of 11.5%. ICT kit showed a low sensitivity of 51.6% in diagnosing HBV but was highly specific (100%) and accurate (94.4%). HBV infection was not associated with sex (χ2: 0.209; p = 0.401). The prevalence of HBV infection was similar in all the age group and HBV infection was not associated (χ2: 2.099; p = 0.914) with age group. All the clinical manifestations were not associated ( p > 0.05) with HBV infection. Blood transfusion, shared items, tattoo marks and history of surgery associated significantly ( p < 0.05) with HBV infections having odd ratios of 4.247, 4.224, 3.134 and 3.195 respectively. The vaccination rate was 55.2% (159/270) and only 3 (1.1%) out of 159 vaccinated subjected contracted the infection (OR: 0.068, p < 0.0001). Conclusions: HBV was prevalent (11.5%) in children below six years old in Enugu metropolis. Moreover, the routinely used ICT test was less reliable than ELISA in diagnosis HBV infection. More so, shared items, blood transfusion, tattooing and history of surgery were potential risk factors while vaccination served as a protective factor against the infection.

Comparative Co-Evolution Analysis Between the HA and NA Genes of Influenza A Virus

Influenza A virus subtypes are determined based on envelope proteins encoded by the hemagglutinin (HA) gene and the neuraminidase (NA) gene, which are involved in attachment to the host, pathogenicity, and progeny production. Here, we evaluated such differences through co-evolution analysis between the HA and NA genes based on subtype and host. Event-based cophylogeny analysis revealed that humans had higher cospeciation values than avian. In particular, the yearly ML phylogenetic trees for the H1N1 and H3N2 subtypes in humans displayed similar topologies between the two genes in humans. Substitution analysis was verifying the strong positive correlation between the two genes in the H1N1 and H3N2 subtypes in humans compared with those in avian and swine. These results provided a proof of principle for the further development of vaccines according to hosts and subtypes against Influenza A virus.

Viral Causes of Lymphoma: The History of Epstein-Barr Virus and Human T-Lymphotropic Virus 1

In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis. Lymphomas have also played an important role in the history of oncoviruses, as both the first human oncovirus (EBV) and the first human retrovirus (HTLV-1) were discovered through isolates taken from patients with unique lymphoma syndromes. The history of the discovery of these 2 key oncoviruses is presented here, and their impact on further medical research, using the specific example of HIV research, is briefly discussed.

Trends of Dengue Disease Epidemiology

Dengue disease is an emerging mosquito-borne viral infection transmitted between humans by Aedes spp. that are distributed mainly in the tropical and subtropical region along with chikungunya and zika diseases. The distribution of dengue disease is influenced by local variation, such as geography, rainfall, temperature, and rapid urbanization or migration. The epidemy of mosquito-borne infection significantly led to increased number of cases and hyperendemicity which induce a more severe form of dengue accompanied by cocirculation of chikungunya and zika. The rapid global spreading of dengue disease created public health burdens that are presently unfulfilled by the absence of specific therapy, simple diagnosis tool for the early phase, and effective and efficient vector control system. This review highlights the current situation of dengue distribution, epidemiology, and new strategies for early dengue diagnosis and risk prediction of severity that can be used to improve oversight and alleviate the heavy burden of the disease.

Prevention of Influenza A(H7N9) and Bacterial Infections in Mice Using Intranasal Immunization With Live Influenza Vaccine and the Group B Streptococcus Recombinant Polypeptides

We investigate the protective effect of combined vaccination based on live attenuated influenza vaccine (LAIV) and group B streptococcus (GBS) recombinant polypeptides against potential pandemic H7N9 influenza infection followed by GBS burden. Mice were intranasally immunized using 107 50% egg infectious dose (EID50) of H7N3 LAIV, the mix of the 4 GBS peptides (group B streptococcus vaccine [GBSV]), or combined LAIV + GBSV vaccine. The LAIV raised serum hemagglutination-inhibition antibodies against H7N9 in higher titers than against H7N3. Combined vaccination provided advantageous protection against infections with A/Shanghai/2/2013(H7N9)CDC-RG influenza and serotype II GBS. Combined vaccine significantly improved bacterial clearance from the lungs after infection compared with other vaccine groups. The smallest lung lesions due to combined LAIV + GBSV vaccination were associated with a prevalence of lung interferon-γ messenger RNA expression. Thus, combined viral and bacterial intranasal immunization using H7N3 LAIV and recombinant bacterial polypeptides induced balanced adaptive immune response, providing protection against potential pandemic influenza H7N9 and bacterial complications.

Human Polyomaviruses: The Battle of Large and Small Tumor Antigens

About 40 years ago, the large and small tumor antigens (LT-Ag and sT-Ag) of the polyomavirus (PyVs) simian vacuolating virus 40 have been identified and characterized. To date, it is well known that all the discovered human PyVs (HPyVs) encode these 2 multifunctional and tumorigenic proteins, expressed at viral replication early stage. The 2 T-Ags are able to transform cells both in vitro and in vivo and seem to play a distinct role in the pathogenesis of some tumors in humans. In addition, they are involved in viral DNA replication, transcription, and virion assembly. This short review focuses on the structural and functional features of the HPyVs’ LT-Ag and sT-Ag, with special attention to their transforming properties.