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Journal of Virology, July 2007, p. 7329, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.01117-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Cytoplasmic Assembly of Herpes Simplex Virus Requires the Function of Cellular ESCRT Proteins

Many families of enveloped RNA viruses utilize the cellular endosomal sorting complexes required for transport (ESCRT) to bud through the plasma membrane during viral egress. Crump et al. (p. 7380-7387) now show that expression of a dominant-negative mutant form of Vps4, a protein crucial for ESCRT function, inhibits cytoplasmic envelopment of herpes simplex virus. This is the first report suggesting a role for ESCRT proteins in the assembly of large, complex DNA viruses.

In Vitro Primary Cell Model for Latent Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) can generate a latent infection that is impervious to current therapies. Robust in vitro primary cell models of latency are lacking. Burke et al. (p. 7424-7434) report the first in vitro model of latent HIV infection in primary thymocytes. Expression of a latent HIV reporter virus could be induced 200-fold from infected thymocytes following cellular activation. Viral gene expression originates from an integrated genome and is highly dependent on NF-{kappa}B. This new model can be utilized to study molecular aspects of latent HIV infection in primary cells.

Apoptotic Signaling Cascade Involved in Poliovirus-Infected Neuroblastoma Cells

Poliovirus is the etiological agent of paralytic polyomyelitis. The main target cell of poliovirus in the central nervous system is the motor neuron. Poliovirus-induced apoptosis of motor neurons appears to contribute to paralysis. Autret et al. (p. 7504-7516) provide evidence that poliovirus induces Bax-dependent apoptosis mediated by early c-Jun NH2-terminal kinase (JNK) activation in neuroblastoma cells. Interestingly, the poliovirus-receptor (CD155) interaction alone is sufficient to induce JNK activation. These findings shed light on the cellular pathways leading to poliovirus neuropathogenicity.

Foxp3+ CD4+ CD25+ Regulatory T Cells and Ocular Infection and Immunity

Homeostasis of the ocular mucosal immune system (OMIS) depends on a balance between the immune response to invading pathogens and immune tolerance to self-antigens. Naturally occurring Foxp3+ CD4+ CD25+ "natural" regulatory T cells (nTreg) regulate these responses. Nesburn et al. (p. 7647-7661) report an abundance of resident nTreg cells in rabbit conjunctiva, the main OMIS T-cell inductive site. These nTreg cells may suppress effector CD4+ and CD8+ T-cell responses to ocular pathogens like herpes simplex virus type 1, thus decreasing immunopathological responses that cause corneal scarring and vision loss. This process also might interfere with immunity to ocular vaccines and therapies.

DNA Vaccination against Cytomegalovirus by Using Conserved, Essential Genes

Cytomegalovirus (CMV) persists in infected host organisms despite strong T-lymphocyte responses that may be skewed by the virus to promote viral persistence rather than clearance. Morello et al. (p. 7766-7775) found that DNA vaccines encoding essential viral genes that are highly conserved, an attractive class of vaccine candidates due to their requirements for expression and sequence conservation, generated antigen-specific CD8+ T cells and provided protection against virus replication. This work suggests that the conserved, essential genes of CMV represent a novel class of targets for CMV vaccine development.

Lethal Severe Acute Respiratory Syndrome-Associated Coronavirus Infection in Aged Mice

Acute respiratory distress syndrome (ARDS) is a serious, life-threatening human condition reported following severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and H5N1 and 1918 influenza virus infections. SARS-CoV originated from zoonotic strains and causes ARDS in the elderly. Rockx et al. (p. 7410-7423) used synthetic biology and reverse genetics to reconstruct a panel of heterologous SARS-CoV isolates, some of which recapitulated the ARDS-associated pathologic findings in an aged rodent model. This work provides heterologous SARS-CoV challenge strains that will allow for vaccine testing against zoonotic virus outbreak strains and help elucidate the molecular mechanisms of virus-induced ARDS in the elderly.


Journal of Virology, July 2007, p. 7329, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.01117-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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