Search

The capacity of respiratory viruses to undergo evolution within the respiratory tract raises the possibility of evolution under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts are potential drivers of viral evolution and development of infectious variants. We showed that intrahost evolution in chronic human parainfluenza virus 3 (HPIV3) infection in immunocompromised individuals elicited mutations that favored viral entry and persistence, suggesting that similar processes may operate across enveloped respiratory viruses. We profiled longitudinal HPIV3 infections from 2 immunocompromised individuals that persisted for 278 and 98 days. Mutations accrued in the HPIV3 attachment protein hemagglutinin-neuraminidase (HN), including the first in vivo mutation in HN's receptor binding site responsible for activating the viral fusion process. Fixation of this mutation was associated with exposure to a drug that cleaves host-cell sialic acid moieties. Longitudinal adaptation of HN was associated with features that promote viral entry and persistence in cells, including greater avidity for sialic acid and more active fusion activity in vitro, but not with antibody escape. Long-term infection thus led to mutations promoting viral persistence, suggesting that host-directed therapeutics may support the evolution of viruses that alter their biophysical characteristics to persist in the face of these agents in vivo., Introduction Human parainfluenza virus 3 (HPIV3) accounts for a large proportion of respiratory illness in humans, especially in children, the elderly, and immunocompromised individuals (1-9), yet there is currently no [...]

Chikungunya virus (CHIKV) is an emerging arbovirus, endemic in many parts of the world, that is spread by travelers and adapts to new mosquito vectors that live in temperate climates. CHIKV replicates in many host tissues and initially causes a self-limiting febrile illness similar to dengue. However, in 30%-40% of cases, CHIKV also causes long-term painful and debilitating muscle and joint pain, the pathogenesis of which remains unknown. In this issue of the JCI, Lentscher et al. engineered a skeletal muscle-restricted CHIKV to show that while musculoskeletal disease requires viral replication in affected muscle, muscular pathology is mediated by host immunological factors. These findings de-link viral replication and disease symptoms, illuminate the virus-host interplay in CHIKV symptomatology, and raise the possibility that immune modulation is a therapeutic option. The results also highlight possible solutions to existing vaccine barriers and provide insights that may apply to other viral diseases., Chikungunya is a uniquely dangerous emerging virus Chikungunya virus (CHIKV) is a member of the Old World Alphavirus genus of the Togaviridae family. It is an arbovirus that causes widespread [...]

We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus-cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure-activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus--cell but not cell-cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus-cell fusion. virology | viral entry | fusion inhibitor | small molecule | lipid membrane www.pnas.org/cgi/doi/10.1073/pnas.0909587107

The article discusses the circulating strain of the Oseltamivir-resistant influenza virus, which seems to be a natural, spontaneously arising variant, and has been a matter of concern for several years. The key aspects of applying a multidrug strategy, which remains the only way of tackling the issue, are highlighted.

The chemical structure of oseltamivir could facilitate the development of resistance mutations that would permit neuraminidase to function, allowing drug-resistant virus to survive and propagate. Several evidences of the potentially serious consequences of oseltamivir resistance in patients with influenza A (H5N1) virus infections are presented.

Treatment of influenza with adamantanes and neuraminidase inhibitors is discussed in detail. Vaccination is known to be the primary strategy for the prevention of influenza but is not considered sufficient to prevent influenza in many cases, and antiviral agents play an important role in constituting a logical method to fight epidemics and pandemics.

Treatment of influenza with adamantanes and neuraminidase inhibitors is discussed in detail. Vaccination is known to be the primary strategy for the prevention of influenza but is not considered sufficient to prevent influenza in many cases, and antiviral agents play an important role in constituting a logical method to fight epidemics and pandemics.

The article discusses medical management and the various drugs that can be employed for the treatment of any kind of influenza infection in humans. It focuses on the need of development of new formulations and guidelines for the appropriate use of drugs in children and people for the treatment of the infection.