Journal of Virology, May 2006, p. 4647, Vol. 80, No. 10
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.10.4647.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
It has not been understood how human papillomaviruses (HPVs) sustain persistent infections in squamous epithelia. Dao et al. (p. 4792-4800) report that the HPV-11 origin-binding protein, E2, colocalizes with the mitotic apparatus in a dynamic manner, possibly via association with a passenger protein. The sequence of the HPV-11 E2 DNA-binding domain conferring this property has been determined and demonstrated to be functionally conserved in the E2 proteins of HPV-16, -18, and bovine papillomavirus type 4. This E2 function would explain equitable segregation of viral DNA in dividing basal keratinocytes and could contribute to high-risk HPV oncogenesis by inducing host chromosomal instability following viral DNA integration.
A Novel Model To Study Kaposi's Sarcoma-Associated Herpesvirus Latency In Vitro and In Vivo
Kaposi's sarcoma-associated herpesvirus infects endothelial cells in vitro but fails to establish stable episomal latency. By performing infection experiments with telomerase-immortalized endothelial cells, An et al. (p. 4833-4846) obtained long-term infected cells that contain episomes at stable copy numbers. Such cultures formed colonies in soft agar and tumors in nude mice. Moreover, while viral gene expression was highly restricted in culture, analysis of mouse tumors revealed some lytic gene expression as is observed in Kaposi's sarcoma tumors. This work provides the first xenograft model for Kaposi's sarcoma, allowing studies of viral latency in mice and evaluation of new therapeutic approaches.
Production of Intracellular Double-Stranded RNA: Not All Viruses Are Equal
Double-stranded RNA (dsRNA) is a highly efficient trigger of the innate immune response. This nucleic acid has been considered a universal pathogen-associated pattern (PAMP) produced by all viruses. Weber et al. (p. 5059-5064) used a dsRNA-specific antibody to systematically test this assumption. The authors detected intracellular dsRNA accumulation for a broad range of viruses with positive-sense RNA or DNA genomes but not for viruses with negative-sense RNA genomes. Thus, dsRNA is in fact an almost universal PAMP for viruses, with the notable exception of the negative-sense RNA viruses.
Systemic Rotavirus Infection
Rotaviruses infect intestinal enterocytes and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. Crawford et al. (p. 4820-4832) now show that viremia occurs in the absence of diarrhea and in the presence of rotavirus-specific antibodies. Rotavirus can infect and replicate in multiple organs and is associated with histopathological changes in the liver and lungs. These findings alter the previously accepted concept of rotavirus pathogenesis to include not only gastroenteritis but viremia and indicate that rotavirus might cause a broad array of systemic diseases in a number of different organs.
Recombinant DNA/Modified Vaccinia Virus Ankara Vaccine Induces Human Immunodeficiency Virus-Specific T Cells in Healthy Vaccinees
Studies using both human and primate models suggest that vaccines inducing human immunodeficiency virus (HIV)-specific T cells may successfully protect against HIV-1 infection or mediate viral control. Goonetilleke et al. (p. 4717-4728) show that vaccination with recombinant DNA/modified vaccinia virus Ankara (MVA) vaccines expressing Gag and an HIV-specific cytotoxic T-lymphocyte epitope string induced multifunctional HIV-specific T cells in all healthy subjects tested. This study demonstrates that recombinant DNA/MVA vaccination regimens induce higher levels of T cells in more vaccinees than immunization with recombinant MVA alone.
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