Journal of Virology, April 2009, p. 3419, Vol. 83, No. 8
0022-538X/09/$08.00+0 doi:10.1128/JVI.00366-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Functions of Human Cytomegalovirus gBPhenotypic complementation of mutant viruses with deletions in essential genes has been routine for most herpesviruses for many years. However, this strategy has not been possible for human cytomegalovirus (HCMV) essential glycoproteins due to the restricted cellular tropism and long replication cycle of this virus. Using retroviral transduction, Isaacson and Compton (p. 3891-3903) have succeeded in propagating a glycoprotein B (gB) deletion HCMV mutant. Analysis of this virus shows that HCMV gB is required for virus-cell and cell-cell fusion but dispensable for attachment, assembly, and egress. This new genetic system will now allow for detailed structure-function analyses of other essential HCMV gene products.
Human Rhinovirus Type 2 RNA Penetration and Transport in the Cytoplasm
For nonenveloped viruses, the driving forces for genome penetration into the cytoplasm are poorly understood. In the case of human rhinovirus type 2, the RNA genome penetrates through a pore in the endosomal membrane. Berka et al. (p. 3778-3787) show that this process is stimulated by cytoplasmic negative membrane potential. Brabec-Zaruba et al. (p. 3770-3777) tracked the uncoated RNA by fluorescence in situ hybridization. Together, these studies demonstrate the rapid arrival of viral RNA in the cytosol, followed by microtubule-independent transport to the perinuclear area, which serves as the site of viral replication.
Gamma Interferon-Mediated Virus Clearance from Neurons Is Dependent on Jak/Stat Signaling
Clearance of virus from infected neurons during recovery from encephalitis requires a noncytolytic process. T-cell production of gamma interferon (IFN-
) contributes to clearance, but the mechanism is not known. Using cultured differentiated neurons previously infected with Sindbis virus, Burdeinick-Kerr et al. (p. 3429-3435) found that IFN- induces prolonged activation of Stat-1 and transient activation of Stat-5. IFN--mediated decrease in viral replication, improved neuronal survival, and Stat activation are prevented by an inhibitor of Jak kinase. These findings demonstrate that activation of the Jak/Stat pathway is the primary mechanism for IFN--induced clearance of Sindbis virus from mature neurons.
Broadly Neutralizing Human Immunodeficiency Virus Antibodies Purified from Human Sera
Humoral system-based vaccine strategies are aimed at inducing antibodies with neutralization breadth and potency similar to that of human immunodeficiency virus (HIV)-specific monoclonal antibody (MAb) 2F5. However, potent and broadly reactive neutralizing antibodies rarely develop in HIV-1-infected persons, and few of these antibody specificities have been defined. Although MAb 2F5 was derived from pooled primary cells, antibodies with similar properties have not been identified in human sera. Shen et al. (p. 3617-3625) identified and purified neutralizing 2F5 epitope-binding antibodies from a patient's serum. These data demonstrate that 2F5 epitope neutralizing antibodies, although very rare, can be elicited and contribute to neutralization of diverse HIV-1 strains.
Antiviral Immunity Elicited by a Bacterial Vaccine
Unexpected T-cell-dependent heterologous immunity against unrelated viruses can occur in humans and mice and has been linked to cross-reactive CD8+ T cells. Mathurin et al. (p. 3528-3539) demonstrate heterologous immunity against a poxvirus, vaccinia virus (VV), in mice immunized against the bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis, used as a vaccine against tuberculosis. This immunity was mediated by BCG-induced memory CD4+ T cells, which synthesize gamma interferon soon after VV infection and restrict VV replication by 10- to 100-fold. These findings indicate that heterologous immunity can occur via different mechanisms and that vaccination may provide a degree of immunity against unrelated pathogens.
Journal of Virology, April 2009, p. 3419, Vol. 83, No. 8
0022-538X/09/$08.00+0 doi:10.1128/JVI.00366-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
| ||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»