Porphyromonas gingivalis induces CCR5-dependent transfer of infectious HIV-1 from oral keratinocytes to permissive cells

<p>Abstract</p> <p>Background</p> <p>Systemic infection with HIV occurs infrequently through the oral route. The frequency of occurrence may be increased by concomitant bacterial infection of the oral tissues, since co-infection and inflammation of some cell types increases HIV-1 replication. A putative periodontal pathogen, <it>Porphyromonas gingivalis </it>selectively up-regulates expression of the HIV-1 coreceptor CCR5 on oral keratinocytes. We, therefore, hypothesized that <it>P. gingivalis </it>modulates the outcome of HIV infection in oral epithelial cells.</p> <p>Results</p> <p>Oral and tonsil epithelial cells were pre-incubated with <it>P. gingivalis</it>, and inoculated with either an X4- or R5-type HIV-1. Between 6 and 48 hours post-inoculation, <it>P. gingivalis </it>selectively increased the infectivity of R5-tropic HIV-1 from oral and tonsil keratinocytes; infectivity of X4-tropic HIV-1 remained unchanged. Oral keratinocytes appeared to harbor infectious HIV-1, with no evidence of productive infection. HIV-1 was harbored at highest levels during the first 6 hours after HIV exposure and decreased to barely detectable levels at 48 hours. HIV did not appear to co-localize with <it>P. gingivalis</it>, which increased selective R5-tropic HIV-1 <it>trans </it>infection from keratinocytes to permissive cells. When CCR5 was selectively blocked, HIV-1 <it>trans </it>infection was reduced.</p> <p>Conclusion</p> <p><it>P. gingivalis </it>up-regulation of CCR5 increases <it>trans </it>infection of harbored R5-tropic HIV-1 from oral keratinocytes to permissive cells. Oral infections such as periodontitis may, therefore, increase risk for oral infection and dissemination of R5-tropic HIV-1.</p

Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells

<p>Abstract</p> <p>Background</p> <p>Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner.</p> <p>Results</p> <p>To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells) were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1<it>gag </it>RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Δenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells <it>trans </it>infected co-cultured peripheral blood mononuclear cells (PBMCs) or MOLT4 cells (CD4+ CCR5+) by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also <it>trans </it>infected HIV-1 to permissive cells in a donor-specific manner.</p> <p>Conclusion</p> <p>Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.</p

Between Raetia Secunda and the dutchy of Bavaria: Exploring patterns of human movement and diet.

During the transition from Late Antiquity to the Middle Ages, the Roman Empire dissolved in the West and medieval empires were founded. There has been much discussion about the role that migration played in this transition. This is especially true for the formation of the Baiuvariian tribe and the founding of this tribal dukedom, which took place from the 5th to the 6th century in what is now Southern Bavaria (Germany). In this study, we aimed to determine the extent of immigration during the beginning of this transformation and to shed further light on its character. To achieve this goal, we analyzed stable isotope values of strontium, carbon, and nitrogen from the teeth and bones of over 150 human remains from Southern Germany, dating from around 500 AD. This group of individuals included women with cranial modifications (ACD) which can be found sporadically in the burial grounds of this period. Our results showed an above-average migration rate for both men and women in the second half of the 5th century. They also indicate that a foreign background may also be assumed for the women with ACD. The demonstrably different origins of the immigrants from isotopically diverse regions, and the identification of local differences in detectable migration rate, as well as indication for different timing of residential changes, highlight the complexity of immigration processes and the need for more studies at the regional level

Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection

In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by ≤3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir