Virology, Emerging Diseases & vaccines

Influenza and acute respiratory virus disease is a field of public health of major international importance.  Recent epidemiological events - the 2009 pandemic of H1N1 influenza, first identified in Mexico; the occurrence of human cases of avian influenza A(H7N9) in China; the emergence of Middle East Respiratory Syndrome (MERS-CoV); and ongoing outbreaks of virulent avian influenza A(H5N1) in several countries; continue to highlight the requirement for international collaboration on respiratory virus research and development.  Acute respiratory infections (ARI) impose a significant burden of both morbidity and mortality on children worldwide. In 2000 alone, an estimated 1·9 million children under the age of five died as the result of ARI, accounting for 14% of total mortality in the age group. While most infections are fairly mild, self‐limiting, and confined to the upper respiratory tract, severe illnesses can also occur. Influenza infections can be life‐threatening, mainly among the elderly, yet present a risk for the entire human population in the wake of influenza pandemics. As a result of constant genetic mutations in the influenza virus, the effectiveness of vaccination depends on the continuous monitoring of circulating strains globally.

Viral transmission is the process by which viruses spread between hosts. It includes spread to members of the same host species or spread to different species in the case of viruses that can cross species barriers. Transmissibility within human populations is a key determinant of epidemic potential. Many viruses that can infect humans are not capable of being transmitted by humans; most human transmissible viruses that emerge already have that capability at first human infection or acquire it relatively rapidly. Virus transmission to humans occurs via inhalation of aerosolized virus-contaminated rodent urine, saliva, and feces, rarely by rodent bites. Humans are usually considered as a dead-end host that does not transmit the virus further. For plant viruses, the pathways reviewed are vertical and horizontal transmission via pollen, and horizontal transmission by parasitic plants, natural root grafts, wind-mediated contact, chewing insects, and contaminated water or soil. For insect viruses, they are transmission by plants serving as passive “vectors,” arthropod vectors, and contamination of pollen and nectar.

Viral pathogenesis is the study of the process and mechanisms by which viruses cause diseases in their target hosts, often at the cellular or molecular level. It is a specialized field of study in virology. Pathogenesis is a qualitative description of the process by which an initial infection causes disease. Viral disease is the sum of the effects of viral replication on the host and the host's subsequent immune response against the virus. Viruses are able to initiate infection, disperse throughout the body, and replicate due to specific virulence factors.

Viral genetics is the study of the mechanisms of heritable information in viruses, including genome structure, replication and genetic change. Viruses have been engineered as vectors for gene expression, vaccine development, and gene therapy. Viral genomes encode gene products that modulate host defences, including the immune response, an elaborate system that evolved in large part to protect us against invading microorganisms like viruses. Ideally, pathogens are cleared by immune defences with minimum damage to the host. However, in the process, the immune defences themselves can also cause damage (immunopathology). Viral evolution refers to the heritable genetic changes that a virus accumulates during its life time, which can arise from adaptations in response to environmental changes or the immune response of the host. Because of their short generation times and large population sizes, viruses can evolve rapidly. RNA viruses have high mutation rates that allow especially fast evolution. An example is the evolution of drug resistance in HIV.  Viruses are believed to have played important roles in the evolution of cellular organisms. Though viruses aren’t technically living – they need a host organism in order to reproduce – they are subject to evolutionary pressures. The recent development of potent antiviral drugs not only has raised hopes for effective treatment of infections with HIV or the hepatitis B virus, but also has led to important quantitative insights into viral dynamics in vivo. Viral dynamics include virus population dynamics, the role of the immune system in limiting virus abundance, the dynamics of viral drug resistance.

Molecular virology refers to the study of viruses at the molecular level which involves the analysis of genes and gene products of viruses and study their interaction with host (human, plant or animal) cellular proteins. Structural Virology is the molecular mechanism used by viruses to invade host cells establish an infection and ensure that progeny virus particles are released into the environment, all while evading the host's immune defences. Viruses are the smallest self -replicating organisms. Even though individually viruses are rather simple, as a group they are exceptionally diverse in both replication strategies and structures. Many viruses are important human pathogens.

To study the life cycle of human virus, we use various technologies like X-ray crystallography, cryo-electron microscopy. We investigate macromolecular interactions associated with virus cell entry, genome replication, assembly, and maturation. Viruses are very simple enough that we can aspire to understand their biology at a molecular level. Our efforts are directed towards using structural information for the development of anti-viral drugs and vaccines.

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. Hematopoietic stem cell transplantation is the treatment of choice for many hematologic malignancies and genetic diseases. However, viral infections continue to account for substantial post-transplant morbidity and mortality. While antiviral drugs are available against some viruses, they are associated with significant side effects and are frequently ineffective.

Viruses are smaller and simpler in construction than unicellular microorganisms, and they contain only one type of nucleic acid—either DNA or RNA—never both. As viruses have no ribosomes, mitochondria, or other organelles, they are completely dependent on their cellular hosts for energy production and protein synthesis. They replicate only within cells of the host that they infect. Animal virology developed largely from the need to control viral diseases in humans and their domesticated animals. Viruses, like other infectious agents, enter the animal body through one of its surfaces. They then spread either locally on one of the body surfaces or through lymphatic and blood vessels to produce systemic infection. Iridoviridae and African Swine Fever Virus, adenovirus, Papillomavirus and Polyomavirus, herpesvirus are some of the major viruses causing diseases in cattle. At least one major disease of each domestic animal species except sheep is caused by a herpesvirus, including such important diseases as infectious bovine rhinotracheitis, pseudorabies, and Marek's disease. However, there are several approaches to their prevention, control, and eradication. The most generally useful control measure is the use of vaccines.

Viral immunology is simply the study of immune responses to viruses. A prolonged tissue-damaging effect resulting from an immune reaction against viruses is considered immunopathology. Such situations most commonly involve persistent viruses, which are themselves often mildly cytodestructive in the absence of an immune reaction. Chronic tissue damage initiated by viruses can also result in development of an autoreactive and an occasionally oncogenic response.

Clinical Virology incorporates a spectrum of disciplines and information ranging from the X-ray crystallographic structure of viruses and viral proteins to the global socio-economic impact of disease. It encompasses events that include accounts ranging from epidemics impacting history to the identification of new agents and mechanisms of disease. Viruses are important pathogens of the nervous system.

Viral oncology is a subdivision of oncology, in these it is concerned with treatment of  human cancers /tumours with virus particles. Viruses have long been used as tools to understand basic mechanisms of cancer development and progression. Many cellular proteins crucial in oncogenesis and tumour suppression were first discovered by studying tumour viruses. Approximately 20% of all cancers worldwide results from chronic infections, in specific, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. Certainly, the infectious nature of specific tumours has important implications in their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be dynamic, with new significant and original studies on viral oncogenesis and as a translational research from virology for the treatment of cancer. At present, only seven established human tumour viruses are known which include Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8 (HHV-8), and Merkel Cell Polyomavirus (MCPyV)., but numerous human cancers are suspected to have an infectious etiology that has not yet been identified. Discovery of each human tumour virus has spawned a new research field that has contributed to our understanding of infectious tumours and cancer biology.

Sexually transmitted diseases (STDs), also known as sexually transmitted infections or STIs, are very common. STDs don’t always cause symptoms or may only cause mild symptoms, so it is possible to have an infection and not know it. If you are diagnosed with an STD, know that all can be treated with medicine and some can be cured entirely. Chlamydia, Gonorrhea, Hepatitis, Herpes, HIV/AIDS, Human Papillomavirus (HPV) Infection, Syphilis are some of the most common and most prevalent sexually transmitted diseases. Non-bacterial, non-viral organisms that can cause disease in humans include fungi, protozoa, helminths. The most important STD within this category will be discussed in this section, trichomoniasis. Nonviral infections are of special concern in young populations and have more serious consequences in women than in men. With perinatal exposure, newborns are at risk for both minor and major complications, including congenital anomalies, mental impairment, and death. If nonviral STIs are detected early, they can be treated, transmission to others can be eliminated, and sequelae can be averted. Appropriate emotional support and effective counseling are important components of infection management.

Antiviral therapy is one of the most exciting aspects of virology, since it has successfully employed basic science to generate very effective treatments for serious viral infections. Most drugs and vaccines, however, selectively target a single virus, thereby providing a “one drug-one bug” solution. In contrast, broad-spectrum antivirals (BSAs) can cover multiple viruses and genotypes and reduce the likelihood of development of resistance. Therefore, some BSAs can be used for the rapid management of new or drug-resistant viral strains, for a first-line treatment. There are two types of anti-viral therapies depending on the type of virus, they are: "episodic" oral antiviral therapy (where antiviral therapy is used intermittently by the patient during a recurrence), or "suppressive" antiviral therapy (where the antiviral therapy is taken continuously to prevent recurrences).

Human endogenous retroviruses (HERVs) represent footprints of previous retroviral infection and have been termed “fossil viruses”. These viruses are spread through vertical transmission via the germline DNA. The role of HERVS in disease is not well understood. They may play a role in human cancers and autoimmune disease. While in baboons and mice there are ERVs that are transmissible as infectious viruses, this is not the case in humans. Human Endogenous Retroviruses (HERVs) may be triggers of autoimmune rheumatic disease. Most endogenous retroviruses are silent—the genes that they encode are not expressed or are expressed only under restricted conditions, although in some animals one or more endogenous retroviruses are normally expressed during the lifetime of an animal.

The bacteria that exist throughout the human body, known as the microbiome, play a variety of roles in the development of the immune system. This is particularly true during infancy when the microbiome and the immune response are developing in tandem. Most vaccines are administered in early childhood to prevent outbreaks of devastating childhood diseases. A higher relative abundance of the phylum Actinobacteria (oral and parenteral vaccines) and Firmicutes (oral vaccines) was associated with both higher humoral and higher cellular vaccine responses, while a higher relative abundance of the phylum Proteobacteria (oral and parenteral vaccines) and Bacteroidetes (oral vaccines) was associated with lower responses. Subjects whose intestinal microbiota is dominated by Bifidobacterium demonstrated a broader level of adaptive immune response to vaccinations. On the other hand, infants with higher ratios of Enterobacteriales, Pseudomonadales, and Clostridiales in their intestinal microbiota exhibited lower immune response to vaccination.

Immunization is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. Vaccines stimulate the body’s own immune system to protect the person against subsequent infection or disease. In addition to the initial immunization process, it has been found that the effectiveness of immunizations can be improved by periodic repeat injections or "boosters." Immunization is a proven tool for controlling and eliminating life-threatening infectious diseases and is estimated to avert between 2 and 3 million deaths each year. Immunotherapy, also called biologic therapy, is a type of cancer treatment that boosts the body's natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function. Immunotherapeutic agents use or modify immune mechanisms. Use of these agents is rapidly evolving. A number of different classes of immunotherapeutic agents have been developed such as Monoclonal antibodies, Fusion proteins, Soluble cytokine receptors, Recombinant cytokines, Small-molecule mimetics, Cellular therapies.

Vaccine‐induced immunity that is established in advance of virus infection relies primarily on adaptive immune responses for protective efficacy. Critically, vaccination depends on the properties of antigen recognition, activation, expansion, memory, trafficking and the multitude of specialist functions of lymphocytes. The extent to which vaccine‐induced immunity is successful also determines the spread and maintenance of a viral pathogen within a population. Viral vaccines have had profound and enduring consequences for human and animal health; the worldwide eradication of smallpox and rinderpest are testament to their outstanding contribution to modern society.

Neglected tropical diseases (NTDs) are a group of infectious diseases that are considered “neglected” because they have traditionally received relatively little attention from global governments and health organizations. More than 1.5 billion people suffer from one or more NTDs. The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. Vaccine trials in Australia, New Zealand, Argentina, and China confirmed the efficacy of the EG95 recombinant antigen against E. granulosus infection in sheep and other host species. Independent vaccine trials carried out in pigs with the TSOL18 antigen in Mexico, Peru, Honduras, and Cameroon have all achieved 99–100% protection against an experimental challenge infection with T. solium. However there are challenges for further development and implementation of these vaccines.  

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance.  In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. The Mucosal Delivery, Intradermal Vaccination, novel design strategies of nanomaterial carriers for vaccine delivery.

Measles was once an eradicated disease in parts of the world after vaccines were developed and administered in at-risk areas. It is caused by the measles virus (MeV) which is a single stranded RNA virus with genetic diversity based on the nucleoprotein gene, including 24 genotypes. Measles complications which include pneumonia, diarrhea, vomiting and encephalitis are more common among children under five years old and adults. Humans are the only natural hosts of measles virus. However, measles has made a comeback partly fuelled by a growing ‘anti-vax’ sentiment, in which people refuse to vaccinate their children due to false public information. Measles is the most infectious disease in the world, with the capability to spread quickly and in great distance. So far, the disease is in Europe, Asia and the Americas, and threatens to spread further. Cases of measles can be dangerous to both adults and children, and in some instances the disease is deadly. Death rates are one to two in every 1,000 cases, and children are most at risk. It can be prevented by MMR vaccine. The vaccine protects against three diseases: measles, mumps, and rubella. One dose of MMR vaccine is approximately 93% effective at preventing measles; two doses are approximately 97% effective. Almost everyone who does not respond to the measles component of the first dose of MMR vaccine at age 12 months or older will respond to the second dose

Sometimes, an old disease reappears in a new clinical form that may often be severe or fatal. These are known as re-emerging diseases. A series of recent emerging infectious disease outbreaks, including the 2014 Ebola virus disease (EVD) epidemic in West Africa and the continuing Zika virus disease epidemic in the Americas, have underlined the need for better understanding of which kinds of pathogens are most likely to emerge and cause disease in human populations. Emerging infectious diseases caused by numerous micro-organisms have been affecting a region, country and sometimes the entire globe from time to time sporadically or in the form of small outbreaks to global pandemic like swine flu. Many diseases which were once considered to be no longer a threat to the public health have once again begun to re-emerge. Many new and emerging RNA and DNA viruses are zoonotic or have zoonotic origins in an animal reservoir that is usually mammalian and sometimes avian. Not all zoonotic viruses are transmissible (directly or by an arthropod vector) between human hosts. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests.

“An emerging infectious disease (EID) is one that has appeared and affected a population for the first time, or has existed previously but is rapidly increasing, either in terms of the number of new cases within a population, or its spread to new geographical areas” One Health is defined as “a collaborative, multisectoral, and transdisciplinary approach—working at local, regional, national, and global levels—with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants and their shared environment. More than half of the known pathogens infectious to humans are shared with animals (“zoonotic” diseases), either via recurring transmission (e.g., rabies or plague) or from an initial spillover event (as is suspected with HIV/AIDS, which genetic analyses suggest probably originally emerged from great apes through contact during hunting or butchering). Public health topics with a One Health scope are as follows: