Current Opinion in Virology

Over the last decade, the emergence of several zoonotic viruses has demonstrated that previously unknown or neglected pathogens have the potential to cause epidemics and therefore to pose a threat to global public health. Even more concerning are the estimated 1.7 million still-undiscovered viruses present in the natural environment or 'global virome', with many of these as-yet uncharacterized viruses predicted to be pathogenic for humans. Thus, in order to mitigate disease emergence and prevent future pandemics, it is crucial to identify the global extent of viral threats to which humans may become exposed...

The continued pressure of COVID-19 on public health worldwide underlines the need for a better understanding of the mechanisms of disease caused by severe acute respiratory syndrome coronavirus-2. Though many animal models are readily available for use, the nonhuman primate (NHP) models are considered the gold standard in recapitulating disease progression in humans. In this review, we highlight the relevant research since the beginning of the pandemic to critically evaluate the importance of this model. We characterize the disease's clinical manifestations, aspects of viral replication and shedding, induction of the host's immune response, and pathological findings that broaden our understanding of the importance of NHPs in research to strengthen our public health approach to the pandemic...

No abstract text is available yet for this article.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic virus able to infect humans and multiple nonhuman animal species. Most natural infections in companion, captive zoo, livestock, and wildlife species have been related to a reverse transmission, raising concern about potential generation of animal reservoirs due to human-animal interactions. To date, American mink and white-tailed deer are the only species that led to extensive intraspecies transmission of SARS-CoV-2 after reverse zoonosis, leading to an efficient spread of the virus and subsequent animal-to-human transmission...

An estimated 257 million people are chronic carriers of hepatitis-B virus (HBV) infection, which resulted in around 1 million deaths, mainly due to hepatocellular carcinoma (HCC). Long-term nucleotide analog treatment of HBV infection is associated with favorable prognosis, no disease progression, and a reduction of HCC risk, but lifelong treatments are required. A better understanding of HBV replication cycle and the host immune response will likely improve the identification of new targets for drug development...

As a group, influenza-A viruses (IAV) infect a wide range of animal hosts, however, they are constrained to infecting selected host species by species-specific interactions between the host and virus, that are required for efficient replication of the viral RNA genome. When IAV cross the species barrier, they acquire mutations in the viral genome to enable interactions with the new host factors, or to compensate for their loss. The viral polymerase genes polymerase basic 1, polymerase basic 2, and polymerase-acidic are important sites of host adaptation...

SARS coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, emerged in China in December 2019. Vaccines developed were very effective initially, however, the virus has shown remarkable evolution with multiple variants spreading globally over the last three years. Nowadays, newly emerging Omicron lineages are gaining substitutions at a fast rate, resulting in escape from neutralization by antibodies that target the Spike protein. Tools to map the impact of substitutions on the further antigenic evolution of SARS-CoV-2, such as antigenic cartography, may be helpful to update SARS-CoV-2 vaccines...

Hepatitis-C virus (HCV) chronically infects 58 million individuals worldwide with variable disease outcome. While a subfraction of individuals exposed to the virus clear the infection, the majority develop chronic infection if untreated. Another subfraction of chronically ill proceeds to severe liver disease. The underlying causes of this interindividual variability include genetic polymorphisms in interferon genes. Here, we review available data on the influence of genetic or pharmacological perturbation of HCV host dependency factors on the clinically observed interindividual differences in disease outcome...

Microtubule transport and nuclear import are functionally connected, and the nuclear pore complex (NPC) can interact with microtubule motors. For several alphaherpesvirus proteins, nuclear localization signals (NLSs) and their interactions with specific importin-α proteins have been characterized. Here, we review recent insights on the roles of microtubule motors, capsid-associated NLSs, and importin-α proteins for capsid transport, capsid docking to NPCs, and genome release into the nucleoplasm, as well as the role of importins for nuclear viral transcription, replication, capsid assembly, genome packaging, and nuclear capsid egress...

No abstract text is available yet for this article.

Gene duplications are a major source of genetic diversity and evolutionary innovation. Newly formed, duplicated genes can provide a selection advantage in constantly changing environments. One such example is the arms race of HIV and related lentiviruses with innate immune responses of their hosts. In recent years, it has become clear that both sides have benefited from multiple gene duplications. For example, amplifications of antiretroviral factors such as apolipoprotein-B mRNA-editing enzyme catalytic polypeptide-3 (APOBEC3), interferon-induced transmembrane protein (IFITM), and tripartite motif-containing (TRIM) proteins have expanded the repertoire of cell-intrinsic defense mechanisms and increased the barriers to retroviral replication and cross-species transmission...

The effectiveness of early COVID-19 vaccines in reducing the severity of the disease has led to a focus on developing next-generation vaccines that can prevent infection and transmission of the virus. One promising approach involves the induction of mucosal immunity through nasal administration and a variety of mucosal vaccine candidates using different platforms are currently in development. Live-attenuated viruses, less pathogenic versions of SARS-CoV-2, have promising features as a mucosal vaccine platform and have the potential to induce hybrid immunity in individuals who have already received mRNA vaccines...

Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome. Properties such as the ease of genome modification, respiratory tract tropism, and self-limiting replication in mammals make NDV an attractive vector for vaccine development. Experimental NDV-based vaccines against multiple human and animal pathogens elicited both systemic and mucosal immune responses and were protective in preclinical animal studies, but their real-life efficacy remains to be demonstrated. Only recently, the first results of clinical trials of NDV-based vaccines against SARS-CoV-2 became available, highlighting the challenges that need to be overcome to fully realize the potential of NDV as a platform for the rapid development of economically affordable and effective mucosal vaccines...

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past ten years, there has been substantial progress in the development of new vaccine candidates and therapies against these viruses. These advancements were guided by the structural elucidation of the major surface glycoproteins for these viruses, the fusion (F) protein and attachment (G) protein. The identification of immunodominant epitopes on the RSV F and hMPV F proteins has expanded current knowledge on antibody-mediated immune responses, which has led to new approaches for vaccine and therapeutic development through the stabilization of pre-fusion constructs of the F protein and pre-fusion-specific monoclonal antibodies with high potency and efficacy...

Kaposi sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8, is an oncogenic herpesvirus. Its latency-associated nuclear antigen (LANA) is essential for the persistence of KSHV in latently infected cells. LANA mediates replication of the latent viral genome during the S phase of a dividing cell and partitions episomes to daughter cells by attaching them to mitotic chromosomes. It also mediates the establishment of latency in newly infected cells through epigenetic mechanisms and suppresses the activation of the productive replication cycle...

The prospect of identifying high-risk viruses and designing interventions to pre-empt their emergence into human populations is enticing, but controversial, particularly when used to justify large-scale virus discovery initiatives. We review the current state of these efforts, identifying three broad classes of predictive models that have differences in data inputs that define their potential utility for triaging newly discovered viruses for further investigation. Prospects for model predictions of public health risk to guide preparedness depend not only on computational improvements to algorithms, but also on more efficient data generation in laboratory, field and clinical settings...

The filovirus vaccine and the therapeutic monoclonal antibody (mAb) research have made substantial progress. However, existing vaccines and mAbs approved for use in humans are specific to Zaire ebolavirus (EBOV). Since other Ebolavirus species are a continuing threat to public health, the search for broadly protective mAbs has drawn attention. Here, we review viral glycoprotein-targeting mAbs that have proved their broader protective efficacy in animal models. MBP134AF , the most advanced of these new-generation mAb therapies, has recently been deployed in Uganda during the Sudan ebolavirus outbreak...

Cellular cryo-electron tomography (cryo-ET) offers 3D snapshots at molecular resolution capturing pivotal steps during viral infection. However, tomogram quality depends on the vitrification level of the sample and its thickness. In addition, mandatory inactivation protocols to assure biosafety when handling highly pathogenic viruses during cryo-ET can compromise sample preservation. Here, we focus on different strategies applied in cryo-ET and discuss their advantages and limitations with reference to severe acute respiratory syndrome coronavirus 2 studies...

To cause pandemics, zoonotic respiratory viruses need to adapt to replication in and spread between humans, either via (indirect or direct) contact or through the air via droplets and aerosols. To render influenza A viruses transmissible via air, three phenotypic viral properties must change, of which receptor-binding specificity and polymerase activity have been well studied. However, the third adaptive property, hemagglutinin (HA) acid stability, is less understood. Recent studies show that there may be a correlation between HA acid stability and virus survival in the air, suggesting that a premature conformational change of HA, triggered by low pH in the airways or droplets, may render viruses noninfectious before they can reach a new host...

The COVID-19 pandemic caused by SARS-CoV-2 has led to hundreds of millions of infections and millions of deaths, however, human monoclonal antibodies (mAbs) can be an effective treatment. Since SARS-CoV-2 emerged, a variety of strains have acquired increasing numbers of mutations to gain increased transmissibility and escape from the immune response. Most reported neutralizing human mAbs, including all approved therapeutic ones, have been knocked down or out by these mutations. Broadly neutralizing mAbs are therefore of great value, to treat current and possible future variants...