To investigate transmission of human herpesvirus (HHV)-8, 2546 mother-child pairs were recruited from rural clinics in South Africa and were tested f

Several viruses are recognized as the direct or indirect causative agents of human tumors and other severe human diseases. Vascular endothelial growth factor (VEGF) is identified as a principal proangiogenic factor that enhances the production of new blood vessels from existing vascular network. Therefore, oncogenic viruses such as Kaposi’s sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) and non-oncogenic viruses such as herpes simplex virus (HSV-1) and dengue virus, which lack their own angiogenic factors, rely on the recruitment of cellular genes for angiogenesis in tumor progression or disease pathogenesis. This review summarizes how human viruses exploit the cellular signaling machinery to upregulate the expression of VEGF and benefit from its physiological functions for their own pathogenesis. Understanding the interplay between viruses and VEGF upregulation will pave the way to design targeted and effective therapeutic approaches for viral oncogenesis and severe diseases.

Methicillin resistant Staphylococcus aureus (MRSA) constitutes a major global health concern causing hospital and community acquired infections. A wide diversity of MRSA genotypes are circulating in geographically related regions. Therefore understanding the molecular epidemiology of MRSA is fundamental to design control and clearance measures. A total of 106 MRSA isolates from infection (51) and carrier colonization sites (55) are characterized genetically based on SCCmec and MLST genotyping methods in addition to detection of PVL, TSST-1 and enterotoxins. Sccmec-IV was the most frequently detected genotype (77.3%) followed by genotype V (13.2%) and III (9.4%). SCCmec-IVa was more prevalent among the carrier group (p value 0.002). CC80 was the most commonly identified clonal complex (CC). CC6 and CC22 were significantly more prevalent among the carrier group (p value 0.02 and 0.01, respectively). PVL was highly prevalent among the isolates (58.5%). PVL was detected in 70.6% of isolates from infection sites and 47.3% of isolates from carriers. All strains were sensitive to vancomycin, however, MRSA strains isolated from infection sites had significantly higher MICs compared to strains isolated from carrier colonization sites (p value 0.021). Five new sequence types mainly from the carrier group were identified and described in the study. MRSA population is genetically very diverse among carriers and infected individuals. With SCCmec type IV being most prevalent, this suggests a community origin of most MRSA strains. Therefore very well designed surveillance and clearance strategies should be prepared to prevent emergence and control spread of MRSA in the community.

Most human cytomegalovirus (HCMV) genes are highly conserved in sequence among strains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXC chemokine, and UL139, which is predicted to encode a membrane glycoprotein. The sequences of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North America. UL146 is hypervariable throughout, whereas variation in UL139 is concentrated in a sequence encoding a potentially highly glycosylated region. The UL146 sequences fell into 14 genotypes, as did all previously reported sequences. The UL139 sequences grouped into 8 genotypes, and all previously reported sequences fell into a subset of these. There were minor differences among continents in genotypic frequencies for UL146 and UL139, but no clear geographical separation, and identical nucleotide sequences were represented among communities distant from each other. The frequent detection of multiple genotypes indicated that mixed infections are common. For both genes, the degree of divergence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and the mode of evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selection was detected marginally at best. No evidence was found for linkage disequilibrium. The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times. J. Med. Virol. 80:1615–1623, 2008.

Rationale: In addition to Kaposi's sarcoma, Kaposi's sarcoma–associated herpesvirus (KSHV or HHV-8) has been associated with two other diseases: primary effusion lymphoma and the plasma cell variant of multicentric Castleman's disease. Recently, evidence of KSHV infection was reported in plexiform lesions of idiopathic pulmonary arterial hypertension (IPAH) as well as in adjacent parenchyma and bronchial epithelial cells. Objectives: To further investigate a possible association of KSHV and pulmonary arterial hypertension. Methods and Measurements: Twenty-six lungs explanted from German patients suffering from IPAH were tested for the presence of KSHV antigen and genomes by immunohistochemistry (IHC) and polymerase chain reaction (PCR). Main Results: When stained with a commercial monoclonal antibody directed against the latency-associated nuclear antigen of KSHV, LANA-1, a positive signal reminiscent of the “speckled” nuclear pattern typical of latently KSHV-infected cells was found in 16 (61.5%) cases. Alveolar and bronchial epithelial cells in areas of unremarkable lung tissue, but not cells within the plexiform lesions, were the predominantly stained cell types. Different KSHV-PCR assays (based on orf26, orfK6, and orf72) performed on samples that had tested positively in IHC, however, could not confirm KSHV infection, indicating that the IHC signal was not due to KSHV infection. One IHC-negative patient tested positive by PCR. A PCR based on consensus degenerate hybrid oligonucleotide primers (CODEHOP) to detect yet unknown γ-herpesviruses did not reveal any specific sequences. Conclusions: KSHV is unlikely to play a role in the pathogenesis of IPAH.

Kaposi's sarcoma herpesvirus (KSHV) Fas-associated death domain (FADD)-like interleukin-1 beta-converting enzyme (FLICE)-inhibitory protein, vFLIP, has antiapoptotic properties, is a potent activator of the NF-κB pathway, and induces the formation of endothelial spindle cells, the hallmark of Kaposi's sarcoma, when overexpressed in primary endothelial cells. We used a reverse genetics approach to study several functions of KSHV vFLIP in the context of the whole viral genome. Deletion of the gene encoding vFLIP from a KSHV genome cloned in a bacterial artificial chromosome (BAC) reduced the ability of the virus to persist and induce spindle cell formation in primary human umbilical vein endothelial cells (HUVECs). Only a few, mainly interferon (IFN)-responsive, genes were expressed in wild-type KSHV (KSHV-wt)-infected endothelial cells at levels higher than those in KSHV-ΔFLIP-infected endothelial cells, in contrast to the plethora of cellular genes induced by overexpressed vFLIP. In keeping with this observation, vFLIP induces the phosphorylation of STAT1 and STAT2 in an NF-κB-dependent manner in endothelial cells. vFLIP-dependent phosphorylation of STAT1 and STAT2 could be demonstrated after endothelial cells were infected with KSHV-wt, KSHV-ΔFLIP, and a KSHV-vFLIP revertant virus. These findings document the impact of KSHV vFLIP on the transcriptome of primary endothelial cells during viral persistence and highlight the role of vFLIP in the activation of STAT1/STAT2 and STAT-responsive cellular genes by KSHV.