Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells.

HIV-1 subverts antigen processing in dendritic cells (DCs) resulting in viral uptake, infection, and transfer to T cells. Although DCs bound monomeric gp120 and HIV-1 similarly, virus rarely colocalized with endolysosomal markers, unlike gp120, suggesting HIV-1 alters endolysosomal trafficking. Virus within DC intracellular compartments rapidly moved to DC-CD4+ lymphocyte synapses when introduced to CD4+ lymphocyte cultures. Although viral harboring and transfer from nonlysosomal compartments was transient, given DC-associated virus protein, nucleic acids, and infectious HIV-1 transfer to CD4+, lymphocytes decayed within 24 hours. However a second long-term transfer phase was apparent in immature DCs after 48 hours as a zidovudine-sensitive rise in proviral DNA. Therefore, DCs transfer HIV-1 to CD4+ lymphocytes in 2 distinct phases. Immature and mature DCs first divert virus from the endolysosomal pathway to the DC-T-cell synapse. Secondly, the later transfer phase from immature DCs is through de novo HIV-1 production. Thus, the controversy of DCs being infected or not infected for the mechanics of viral transfer to CD4+ lymphocytes can be addressed as a function of time.

The role of dendritic cell C-type lectin receptors in HIV pathogenesis.

Dendritic cells play a major role in HIV pathogenesis. Epithelial dendritic cells appear to be one of the first cells infected after sexual transmission and transfer of the virus to CD4 lymphocytes, simultaneously activating these cells to produce high levels of HIV replication. Such transfer may occur locally in inflamed mucosa or after dendritic cells have matured and migrated to local lymph nodes. Therefore, the mechanism of binding, internalization, infection and transfer of HIV to CD4 lymphocytes is of great interest. Recently, the role of the C-type lectin DC-SIGN as a dendritic cell receptor for HIV has been intensively studied with in vitro monocyte-derived dendritic cells. However, it is clear that other C-type lectin receptors such as Langerin on Langerhan cells and mannose receptor on dermal dendritic cells are at least equally important for gp120 binding on epithelial dendritic cells. C-type lectin receptors play a role in virus transfer to T cells, either via de novo infection ("cis transfer") or without infection ("in trans" or transinfection). Both these processes are important in vitro, and both may have a role in vivo, although the low-level infection of immature dendritic cells may be more important as it leads to R5 HIV strain selection and persistence of virus within dendritic cells for at least 24 h, sufficient for these cells to transit to lymph nodes. The exact details of these processes are currently the subject of intense study.

Norwalk-like virus 95/96-US strain is a major cause of gastroenteritis outbreaks in Australia.

Norwalk-like viruses (NLVs) were detected using a nested reverse transcriptase-polymerase chain reaction (RT-PCR) with primers directed to the RNA polymerase region. Samples were examined from 11 separate outbreaks of gastroenteritis and five sporadic cases of childhood gastroenteritis between 1997 and 2000. Phylogenetic analysis of the 298 bp sequences showed that all strains belong to NLV genogroup II and the majority of the sequenced isolates (30/36) were members of the 95/96-US subset of strains associated with outbreaks recorded worldwide between 1995 and 1996. This was confirmed by analysis of the full length capsid region of a representative Australian isolate. This study demonstrates the usefulness of targeting primers for NLVs to the predominant circulating genotype(s) and confirms the spread of this subtype globally, including the Southern Hemisphere.