Journal of Virology, December 2005, p. 14471-14472, Vol. 79, No. 23
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.23.14471-14472.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Novel MMTV RNA Export Protein IdentifiedMouse mammary tumor virus (MMTV) previously has been classified as a simple retrovirus with an unknown mechanism for export of unspliced and partially spliced RNAs. Mertz et al. (p. 14737-14747) report a novel protein called regulator of export of MMTV mRNA (Rem). Rem facilitates nuclear export of unspliced RNAs via the Crm1 pathway using a unique, self-regulatory C terminus. The identification of an accessory protein encoded by a doubly spliced RNA suggests that MMTV is the first murine complex retrovirus to be documented. Manipulation of the MMTV genome may provide mouse models for human retroviral diseases, such as AIDS.
SARS-CoV Group-Specific ORFs Encode Nonessential Functions for Replication in Cell Culture and Mice
The highly pathogenic SARS coronavirus (SARS-CoV) encodes several unique group-specific open reading frames (ORFs). The functions of these ORFs in replication and pathogenesis are unknown. Yount et al. (p. 14909-14922) now show that several of the SARS-CoV group-specific ORFs can be deleted without altering replication in culture or in mice. Either the group-specific ORFs play little role in replication in vivo or the mouse model is insufficient for discerning the role of the group-specific ORFs in disease pathogenesis.
High-Level Herpes Simplex Virus Gene Expression during Reactivation Requires Secondary Infections
Herpes simplex virus (HSV) gene expression during reactivation from latency is sensitive to inhibition of viral DNA synthesis. This and other observations have led to the suggestion that regulation of gene expression during reactivation differs from that during productive infection. Pesola et al. (p. 14516-14525) found that inhibiting viral encapsidation or viral DNA synthesis results in similar reductions in expression of immediate-early and early genes after reactivation of latently infected ganglia. This finding is consistent with the rapid detection of infectious virus following a reactivating stimulus. Thus, high-level HSV gene expression during reactivation appears to require secondary infections, which has implications for viral regulatory mechanisms.
Cytomegalovirus Engages a DNA Damage Response Player To Inhibit Apoptosis
Cytomegalovirus (CMV) evades the host cell response to infection by expressing vMIA, a mitochondrion-localized inhibitor of apoptosis that lacks sequence relatedness to Bcl-2 proteins but may act at a similar level. Smith and Mocarski (p. 14923-14932) show that vMIA activity depends on an amphipathic 
-helical motif at the carboxyl terminus that specifically binds DNA damage response protein GADD45. Addition of GADD45 family proteins to cells increases the potency of vMIA- or Bcl-xL-mediated cell death suppression. Concordantly, inhibition of GADD45 function compromises vMIA activity. This work suggests a link between the DNA damage response and suppression of apoptosis by viral as well as cellular inhibitors.
Viral Env Determines HTLV Distinct T-Cell Transformation Tropism
HTLV-1 and HTLV-2 are highly related complex retroviruses that infect various cell types but only immortalize or transform distinct T-lymphocyte populations in culture. HTLV-1 has a preferential tropism for CD4+ T lymphocytes, whereas HTLV-2 preferentially transforms CD8+ T lymphocytes. Xie and Green (p. 14536-14545) used infectious HTLV-1 and HTLV-2 recombinants to identify the viral env gene as a major genetic determinant of the distinct HTLV T-cell transformation tropism in vitro. These findings provide strong evidence implicating a postentry contribution of Env to transformation tropism and ultimately the distinct pathobiologies associated with HTLV-1 and HTLV-2 infections.
A Model for Human Papillomaviruses and Skin Cancer
Although it has been clearly demonstrated that high-risk human papillomaviruses (HPVs) of the genus alpha are associated with cervical cancer, the role of HPV types of the genus beta in human skin cancer is debated. Dong et al. (p. 14899-14908) show that transgenic mice expressing oncogenes from genus beta HPV type 38 in the skin display hyperplasia, dysplasia, and an increased susceptibility to chemical-induced carcinogenesis. This work provides further support for the role of HPV type 38 and possibly other HPV types of this genus in human skin carcinogenesis.
Differentiation State of Human Airway Epithelia Influences ACE2 Expression and Susceptibility to SARS Coronavirus Infection
Human airway epithelial cells are a site of SARS coronavirus (SARS-CoV) replication during the course of SARS-CoV infection in vivo. Jia et al (p. 14614-14621) discovered that the state of airway epithelial cell differentiation positively correlates with ACE2 receptor expression and SARS-CoV infection and replication in these cells. ACE2 is most abundantly expressed on the apical surface of ciliated cells, and SARS-CoV enters and exits predominantly from the apical surface of polarized airway epithelia. This work provides new insights into the pathogenesis of pulmonary disease caused by SARS-CoV and the more common NL63-CoV and suggests new targets for coronavirus therapeutics.
Interaction of Rotavirus with Myeloid Human Dendritic Cells
The human immune response to rotavirus is poorly understood. Children infected with rotavirus have very few circulating rotavirus-specific T cells that secrete gamma interferon. Narváez et al. (p. 14526-14535) now show that rotavirus infects small numbers of immature dendritic cells. Rotavirus is not a strong stimulus for dendritic cell maturation but can prime these cells to stimulate allogeneic naive CD4+ T cells to secrete Th1 cytokines. Further work is needed to establish why rotavirus does not induce a strong Th1 response in acutely infected children.
Pathogenesis of Influenza Viruses with the Haemagglutinin and Neuraminidase of the 1918 Pandemic Virus
Histopathological analyses of lung tissues from individuals who died from primary influenza pneumonia in 1918 reveal heavy infiltrates of leukocytes. The basis of the severe pulmonary damage caused by the 1918 pandemic influenza virus is largely unknown. Tumpey et al (p. 14933-14944) investigated the pathogenesis in mice of a recombinant influenza virus possessing the 1918 hemagglutinin and neuraminidase. Lung tissue from mice infected with the 1918 recombinant virus displayed a predominant neutrophil infiltrate and a moderate increase in macrophages shortly before death of the infected mice. Using cell depletion techniques, both cell types were found to be crucial in controlling the growth and promoting clearance of this highly virulent virus.
Common Ancestry of Herpesviruses and Tailed DNA Bacteriophages
Evolutionary links between herpesviruses and tailed bacteriophages have been suggested based on similarities in capsid assembly and DNA packaging mechanisms. However, to date, there has been no direct structural evidence for such a relationship. Baker et al. (p. 14967-14970) now show that the arrangement of secondary structural elements in the floor domain of the herpes simplex virus major capsid protein affords a close match with those in the capsid proteins of several tailed bacteriophages. These findings suggest that contemporary viruses may be descended from a relatively small number of ancient progenitors.
Journal of Virology, December 2005, p. 14471-14472, Vol. 79, No. 23
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.23.14471-14472.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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