Current Topics in Microbiology and Immunology

Males and females differ in the outcome of influenza A virus (IAV) infections, which depends significantly on age. During seasonal influenza epidemics, young children (< 5 years of age) and aged adults (65+ years of age) are at greatest risk for severe disease, and among these age groups, males tend to suffer a worse outcome from IAV infection than females. Following infection with pandemic strains of IAVs, females of reproductive ages (i.e., 15-49 years of age) experience a worse outcome than their male counterparts...

SARS-CoV-2 is the causative agent of COVID-19 in humans and has resulted in the death of millions of people worldwide. Similar numbers of infections have been documented in males and females; males, however, are more likely than females to be hospitalized, require intensive care unit, or die from COVID-19. The mechanisms that account for this are multi-factorial and are likely to include differential expression of ACE2 and TMPRSS2 molecules that are required for viral entry into hosts cells and sex differences in the immune response, which are due to modulation of cellular functions by sex hormones and differences in chromosomal gene expression...

Biological sex has wide-ranging impacts on HIV infection spanning differences in acquisition risk, the pathogenesis of untreated infection, impact of chronic treated disease and prospects for HIV eradication or functional cure. This chapter summarizes the scope of these differences and discusses several features of the immune response thought to contribute to the clinical outcomes.

Males and females differ in their susceptibility to develop autoimmunity and allergy but also in their capacity to cope with infections and cancers. Cellular targets and molecular pathways underlying sexual dimorphism in immunity have started to emerge and appeared multifactorial. It became increasingly clear that sex-linked biological factors have important impact on the development, tissue maintenance and effector function acquisition of distinct immune cell populations, thereby regulating multiple layers of innate or adaptive immunity through distinct mechanisms...

Women have a stronger immune response and a higher frequency of most autoimmune diseases than men. While much of the difference between men and women is due to the effect of gonadal hormones, genetic differences play a major role in the difference between the immune response and disease frequencies in women and men. Here, we focus on the immune differences between the sexes that are not downstream of the gonadal hormones. These differences include the gene content of the sex chromosomes, the inactivation of chromosome X in women, the consequences of non-random X inactivation and escape from inactivation, and the states that are uniquely met by the immune system of women-pregnancy, birth, and breast feeding...

Lassa fever is caused by Lassa virus (LASV), an Old World Mammarenavirus that is carried by Mastomys natalensis and other rodents. It is endemic in Sierra Leone, Nigeria, and other countries in West Africa. The clinical presentation of LASV infection is heterogenous varying from an inapparent or mild illness to a fatal hemorrhagic fever. Exposure to LASV is usually through contact with rodent excreta. After an incubation period of 1-3 weeks, initial symptoms such as fever, headache, and fatigue develop that may progress to sore throat, retrosternal chest pain, conjunctival injection, vomiting, diarrhea, and abdominal pain...

Coronaviruses have a broad host range and exhibit high zoonotic potential. In this chapter, we describe their genomic organization in terms of encoded proteins and provide an introduction to the peculiar discontinuous transcription mechanism. Further, we present evolutionary conserved genomic RNA secondary structure features, which are involved in the complex replication mechanism. With a focus on computational methods, we review the emergence of SARS-CoV-2 starting with the 2019 strains. In that context, we also discuss the debated hypothesis of whether SARS-CoV-2 was created in a laboratory...

Members of the family Arenaviridae are classified into four genera: Antennavirus, Hartmanivirus, Mammarenavirus, and Reptarenavirus. Reptarenaviruses and hartmaniviruses infect (captive) snakes and have been shown to cause boid inclusion body disease (BIBD). Antennaviruses have genomes consisting of 3, rather than 2, segments, and were discovered in actinopterygian fish by next-generation sequencing but no biological isolate has been reported yet. The hosts of mammarenaviruses are mainly rodents and infections are generally asymptomatic...

Chronic infection with hepatitis C virus (HCV) is an important contributor to the global incidence of liver diseases, including liver cirrhosis and hepatocellular carcinoma. Although common for single-stranded RNA viruses, HCV displays a remarkable high level of genetic diversity, produced primarily by the error-prone viral polymerase and host immune pressure. The high genetic heterogeneity of HCV has led to the evolution of several distinct genotypes and subtypes, with important consequences for pathogenesis, and clinical outcomes...

Fitness of viruses has become a standard parameter to quantify their adaptation to a biological environment. Fitness determinations for RNA viruses (and some highly variable DNA viruses) meet with several uncertainties. Of particular interest are those that arise from mutant spectrum complexity, absence of population equilibrium, and internal interactions among components of a mutant spectrum. Here, concepts, fitness measurements, limitations, and current views on experimental viral fitness landscapes are discussed...

Viruses are studied at each level of biological complexity: from within-cells to ecosystems. The same basic evolutionary forces and principles operate at each level: mutation and recombination, selection, genetic drift, migration, and adaptive trade-offs. Great efforts have been put into understanding each level in great detail, hoping to predict the dynamics of viral population, prevent virus emergence, and manage their spread and virulence. Unfortunately, we are still far from this. To achieve these ambitious goals, we advocate for an integrative perspective of virus evolution...

Mutation, recombination and pseudo-recombination are the major forces driving the evolution of viruses by the generation of variants upon which natural selection, genetic drift and gene flow can act to shape the genetic structure of viral populations. Recombination between related virus genomes co-infecting the same cell usually occurs via template swapping during the replication process and produces a chimeric genome. The family Geminiviridae shows the highest evolutionary success among plant virus families, and the common presence of recombination signatures in their genomes reveals a key role in their evolution...

The wealth of variability amongst genes controlling immunity against potyviruses in pepper (Capsicum spp.) has been instrumental in understanding plant-virus co-evolution and major determinants of plant resistance durability. Characterization of the eukaryotic initiation factor 4E1 (eIF4E1), involved in mRNA translation, as the basis of potyvirus resistance in pepper initiated a large body of work that showed that recessive resistance to potyviruses and other single-stranded positive-sense RNA viruses resulted from mutations in eukaryotic initiation factors in many plant crop species...

The creation of fitness maps from viral populations especially in the case of RNA viruses, with high mutation rates producing quasispecies, is complex since the mutant spectrum is in a very high-dimensional space. In this work, a new approach is presented using a class of neural networks, Self-Organized Maps (SOM), to represent realistic fitness landscapes in two RNA viruses: Human Immunodeficiency Virus type 1 (HIV-1) and Hepatitis C Virus (HCV). This methodology has proven to be very effective in the classification of viral quasispecies, using as criterium the mutant sequences in the population...

The landscape paradigm is revisited in the light of evolution in simple systems. A brief overview of different classes of fitness landscapes is followed by a more detailed discussion of the RNA model, which is currently the only evolutionary model that allows for a comprehensive molecular analysis of a fitness landscape. Neutral networks of genotypes are indispensable for the success of evolution. Important insights into the evolutionary mechanism are gained by considering the topology of sequence and shape spaces...

Varicella zoster virus (VZV) is a medically important human herpesvirus that has co-evolved with the human host to become a highly successful and ubiquitous pathogen. Whilst it is clear the innate and adaptive arms of the immune response play key roles in controlling this virus during both primary and reactivated infections, it is also apparent that VZV "fights back" by encoding multiple functions that impair a wide range of immune molecules. This capacity to manipulate the immune response is likely to be important in underpinning the success of VZV as a human pathogen...

Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster (HZ), which is commonly accompanied by acute pain and pruritus over the time course of a zosteriform rash. Although the rash and associated pain are self-limiting, a considerable fraction of HZ cases will subsequently develop debilitating chronic pain states termed postherpetic neuralgia (PHN). How VZV causes acute pain and the mechanisms underlying the transition to PHN are far from clear. The human-specific nature of VZV has made in vivo modeling of pain following reactivation difficult to study because no single animal can reproduce reactivated VZV disease as observed in the clinic...

Lassa Fever (LF) is a viral hemorrhagic fever endemic in West Africa. LF begins with flu-like symptoms that are difficult to distinguish from other common endemic diseases such as malaria, dengue, and yellow fever making it hard to diagnose clinically. Availability of a rapid diagnostic test and other serological and molecular assays facilitates accurate diagnosis of LF. Lassa virus therapeutics are currently in different stages of preclinical development. Arevirumab, a cocktail of monoclonal antibodies, demonstrates a great safety and efficacy profile in non-human primates...

Despite considerable momentum in the development of RSV vaccines and therapeutics, there remain substantial barriers to the development and licensing of effective agents, particularly in high-risk populations. The unique immunobiology of RSV and lack of clear protective immunological correlates has held back RSV vaccine development, which, therefore, depends on large and costly clinical trials to demonstrate efficacy. Studies involving the deliberate infection of human volunteers offer an intermediate step between pre-clinical and large-scale studies of natural infection...

Venetian quarantine 400 years ago was an important public health measure. Since 1900 this has been refined to include "challenge" or deliberate infection with pathogens be they viruses, bacteria, or parasites. Our focus is virology and ranges from the early experiments in Cuba with Yellow Fever Virus to the most widespread pathogen of our current times, COVID-19. The latter has so far caused over four million deaths worldwide and 190 million cases of the disease. Quarantine and challenge were also used to investigate the Spanish Influenza of 1918 which caused over 100 million deaths...