Throughout the natural course of human immunodeficiency virus (HIV) infection, follicular dendritic cells (FDCs) trap and retain large quantities of particle-associated HIV RNA in the follicles of secondary lymphoid tissue. We have previously found that murine FDCs in vivo could maintain trapped virus particles in an infectious state for at least 9 months. Here we sought to determine whether human FDCs serve as an HIV reservoir, based on the criteria that virus therein must be replication competent, genetically diverse, and archival in nature. We tested our hypothesis using postmortem cells and tissues obtained from three HIVinfected subjects and antemortem blood samples obtained from one of these subjects. Replication competence was determined using coculture, while genetic diversity and the archival nature of virus were established using phylogenetic and population genetics methods. We found that FDC-trapped virus was replication competent and demonstrated greater genetic diversity than that of virus found in most other tissues and cells. Antiretrovirus-resistant variants that were not present elsewhere were also detected on FDCs. Furthermore, genetic similarity was observed between FDC-trapped HIV and viral species recovered from peripheral blood mononuclear cells obtained 21 and 22 months antemortem, but was not present in samples obtained 4 and 18 months prior to the patient's death, indicating that FDCs can archive HIV. These data indicate that FDCs represent a significant reservoir of infectious and diverse HIV, thereby providing a mechanism for viral persistence for months to years.

Background: Double-stranded (ds) RNA, generated during viral infection, binds and activates the mammalian anti-viral protein kinase PKR, which phosphorylates the translation initiation factor eIF2α leading to the general inhibition of protein synthesis. Although PKR-like activity has been described in fish cells, the responsible enzymes eluded molecular characterization until the recent discovery of goldfish and zebrafish PKZ, which contain Z-DNA-binding domains instead of dsRNAbinding domains (dsRBDs). Fish and amphibian PKR genes have not been described so far.

The evolutionary history of two human malaria parasites, Plasmodium vivax and Plasmodium malariae, remains unresolved. The near genetic identity between human P. vivax and P. malariae, and primate P. simium and P. brasilianum, respectively, suggests that recent host transfers occurred, but questions remain, such as whether the transfer was from humans to New World monkeys or vice versa, and when the transfers occurred. Here, we investigate the phylogenies, haplotype networks, positive selection and genetic diversity among these parasite species by means of four genes. Human P. vivax and primate P. simium recently derived one from the other; at least two host transfers have occurred. Human P. malariae and primate P. brasilianum also have recently derived one from the other by lateral host transfer. The direction of the host transfer cannot be decided in either one of the two pairs of species, owing to the scarcity of available strains from the primate parasites.

Plasmodium vivax causes the most geographically widespread human malaria, accounting annually for 70 -80 million clinical cases throughout the tropical and subtropical regions of the world's continents. We have analyzed the DNA sequences of the Csp (circumsporozoite protein) gene in 24 geographically representative strains of P. vivax and 2 of P. simium, which parasitizes several species of New World monkeys. The Csp sequences are of two types, VK210 and VK247, which differ by three diagnostic amino acid replacements, one in each of the 5 and 3 terminal regions [5 nonrepeat (NR) and 3 NR] of the gene and in an insertion sequence that precedes the 3 NR region. The central region of the gene consists of Ϸ38 repetitive ''motifs,'' which are alternatively four and five amino acids long, which also are diagnostically different between the VK210 and VK247 types. There are very few synonymous substitutions within and between the two types of strains, which we hypothesize reflects that the worldwide spread of P. vivax is very recent. The two P. simium Csp sequences belong one to each of the two VK types and are genetically indistinguishable from the corresponding P. vivax strains, suggesting that at least two host transfers have occurred between humans and New World monkeys. We exclude as unlikely the possibility that the two types of sequences could have independently arisen in humans and platyrrhines by natural selection. There are reasons favoring each of the two possible directions of host transfer between humans and monkeys.circumsporozoite protein ͉ clonal theory ͉ Plasmodium population structure ͉ host-parasite interactions ͉ malaria M alaria's human toll is appalling: 300-500 million clinical cases and 1-3 million deaths per year. Plasmodium falciparum accounts for 80% of human malaria's morbidity and mortality, mostly in sub-Saharan Africa. Most geographically widespread and prevalent in some regions is Plasmodium vivax, which accounts annually for 70-80 million clinical cases across much of the tropics and subtropics of the world.The evolutionary origin of P. vivax has been placed by some authors in Southeast Asia (1-3). However, the high prevalence in sub-Saharan Africa of Duffy negativity (absence of the Duffy blood group antigen) that protects against P. vivax infection has been interpreted as evidence of the African origin of P. vivax (4-6). Most recently, phylogenetic and biogeographical evidence has been advanced supporting a Southeast Asia origin (7-9).Recent investigations have shown a scarcity of selectively neutral genetic polymorphisms in P. vivax (8,10,11), which is consistent with a recent world expansion of P. vivax as a human parasite. The discovery that the platyrrhine parasite P. simium is genetically indistinguishable from P. vivax (2,7,8) manifests that a host transfer between humans and New World monkeys has happened in very recent evolutionary times.The circumsporozoite protein (CSP) has been extensively studied in P. falciparum and other Plasmodium species because of its immune significan...