Triumvir

“ Nondividing cells, such as resting T cells and terminally-differentiated macrophages, are important targets for viral replication during the initial stages of infection, since primary infection of these cell populations contributes to the establishment of virus reservoirs, crucial for subsequent virus spread to lymphoid organs and T-helper lymphocytes [58] . Infection of lymphoid histoculture using human tonsil or splenic tissue showed that Vpr greatly enhances HIV replication in macrophages but did not influence productive infection of proliferating or resting T cells [59] . ”

“ Also, it was found that trypan red was a curative agent only for the infection in mice; on the trypanosome diseases of larger animals, as horses and cattle, it had no curative effect. However, the experience with trypan-red pointed the way to a solution of the difficulty; either a drug must be found which by a single injection would kill every parasite, or several different drugs must be used, which, acting on the same parasite, and thus allowing a combination treatment, would lead to a cure without the danger, to the host, of a single massive dose. ”

“ HIV infection does fall well within the general definition set forth by the regulations, however.
The disease follows a predictable and, as of today, an unalterable course. Once a person is infected with HIV, the [p. 634] virus invades different cells in the blood and in body tissues. Certain white blood cells, known as helper T-lymphocytes or CD4+ cells, are particularly vulnerable to HIV. The virus attaches to the CD4 receptor site of the target cell and fuses its membrane to the cell's membrane. ”

“ The migration reduces the viral presence in other parts of the body, with a corresponding diminution in physical manifestations of the disease. The virus, however, thrives in the lymph nodes, which, as a vital point of the body's immune response system, represents an ideal environment for the infection of other CD4‘ cells. ”

“ Schematic view of the early steps of the HIV-1 infection of a target cell. The functional events in which the Vpr protein is involved are highlighted. Vpr has been shown to play multiple functions during the virus life cycle, including an effect on the accuracy of the reverse-transcription process, the nuclear import of the viral DNA as a component of the pre-integration complex, cell cycle progression, regulation of apoptosis, and the transactivation of the HIV-LTR as well as host cell genes. ”

“ The passage through the crithidial stage is characteristic of the salivary development, and the trypanosome forms just mentioned are derived from the crithidial types. The development in the salivary gland takes from two to five days before the forms are infective.
"9. The fly is never infective until the glands are invaded. Trypanosomes from the proventriculus when injected into a monkey never produce infection. Trypanosomes may be found in the salivary glands as early as the sixteenth day of the cycle. ”

“ Our only chance of doing good here is to find an anti-toxin. I want this spare atoxyl for that."
"But," said Roger, "you cannot make an effective serum from the blood of a man in whom atoxyl is at work. Surely atoxyl only stimulates the phagocytes to eat the trypanosome."
"Quite so," said Lionel. "You're a serumite, I'm not. I am not at all keen on the use of serum for this complaint. I believe that the cure (if there is one) will be got by injecting the patient with dead trypanosomes or very, very weak ones. I'm going to make a special artificial culture of trypanosomes in culture tubes. ”

“ Tuberculosis has often been combated by a single dose of a high potence of Sulphur between the doses of Apis, no Apis being given after the Sulphur, as long as the course of the typhoid symptoms would render it safe to postpone this medicine. I have found it much more difficult to conquer the vaccine-poison, which I have become satisfied by years of observation, constitutes the most universal and most powerful generator of the typhus which is prevailing in our age and which seems unwilling to leave us. ”

“ Like you imply, their equipment is alive. So they work best with life—viruses, germs, vegetable-allergy substances. These are their inventing, developing and brewing bottles—for the numerous strains of Syrtis Fever virus. The living molecule chains split off from the inner tissue walls of the bottles, and grow and multiply in the free fluid. At least, that's how I read it."
"And that is where my lab job begins, Frank," she told him. "Helping develop anti-virus shots—testing them on bits of human tissue, growing in a culture bath. An even partially effective anti-virus isn't found easily. ”

“ Of course, the PIC likely contains cellular factors that participate in both intra-cytoplasmic routing and nuclear translocation of the viral DNA. While actin microfilaments seem to play a role in the early events of infection by acting as a scaffold for the appropriate localization and activation of the RTC [67] , the PIC is tightly associated with microtubular structures in the cytoplasm. An elegant system using Vpr fused to GFP as a probe was developed to follow the movement of the PIC soon after virus entry in living cells [38] . ”

“ This important point is known by the fact, that the improvement which had already commenced, seems to remain stationary; the patient experiences a distressing urging to stool, a burning diarrhœa sets in, and a disproportionate feeling of malaise develops itself. Under these circumstances, a globule of Apis 30 will quiet the patient, and the action of the drug will achieve the cure without any further difficulty, and without much loss of time, unless psora, sycosis, syphilis, or vaccine-virus prevail in the organism, or sulphur, iodine or mercury had been previously given in large doses. ”

“ Initially identified from a yeast two-hybrid screening using Vpr as a bait, the interaction with UNG was confirmed both in vitro and ex vivo in Vpr-expressing cells. While the Trp residue in position 54 located in the exposed loop connecting the second and the third α-helix of HIV-1 Vpr has been shown critical to maintain the interaction with UNG, the Vpr-binding site was mapped within the C-terminal part of UNG2 and occurs through a TrpXXPhe motif. ”

“ To fight the disease successfully it is necessary to kill them before they have passed from the blood, since it is only in the blood that atoxyl, [3] one weapon that we at present possess, produces effects which can to any extent be relied on; in the cerebro-spinal marrow the trypanosomes are comparatively safe from it. A doctor must, therefore, learn to recognise the disease in the early stage, when it first produces fever. ”

“ In any event, a female infected through semen provides a focus of infection for others.
With the possible exception of the uterine changes alluded to in the preceding paragraph, PPV-induced reproductive failure is caused by the direct effect of the virus on the conceptus. In the absence of an immune response, the virus replicates extensively throughout these tissues. By the time the conceptus dies, most of its cells contain large quantities of intracytoplasmic viral antigen that can be demonstrated by IF microscopy. ”

“ It is also known as the human trypanosomiasis of Brazil, South American trypanosomiasis, and Chagas’ disease.
Chagas88 reports two principal forms—acute and chronic. The acute infection is rare, and is characterized by increase in the volume of the thyroid gland, pyrexia, a sensation of crackling in the skin, enlarged lymphatic glands in the neck, axilla, etc., while the liver and spleen are increased in volume. Sclerosis of the thyroid gland is found at autopsy and fatty degeneration of the liver. During an attack of fever, trypanosomes are found in the blood. ”

“ Noting that blockade assays are not true measurements of neutralization, NVB 71.4 has potential as a therapeutic reagent based on its broad GII.4 blockade potential and the fact that it is by nature a human antibody. Clearly, the effectiveness of NVB 71.4 at preventing or treating illness can only be determined empirically. Although one of the blockade-epitope specific mAbs with lower EC50 values/steeper Hill constants may be more effective at select strain neutralization, the breadth of strains neutralized is likely to be limited for these mAbs. ”

“ In agreement, the Vpr-induced G2 arrest correlates with high level of viral replication in primary human T cells.
The determinants of the G2 arrest activity are mainly located in the C-terminal unstructured basic region of HIV-1 Vpr and phosphorylation of the protein is required [99] , [100] . Regulators of the cell cycle, such as cyclin-dependant kinases (CDKs) , control progression through the cell cycle by reversible phosphorylation [101] . The p34/cdc2 CDK associates with cyclin B1 in the G2 phase (for review, see [102] ) to regulate the G2 to M transition. ”

“ Gradually increasing mental deterioration marks the almost invariable course to death. A more virulent type of trypanosomiasis is found in Rhodesia.
In Brazil there is a disease caused by a flagellate, Schizotrypanum cruzi, which resembles a trypanosome and is transmitted by a bug, Lamus megistus. The disease runs an acute course with a high fever and great mortality in infants showing chiefly manifestations of involvement of brain or thyroid gland. In adults it runs a chronic course showing neurological manifestations or signs of myxoedema or even of Addison’s disease. ”

“ A drug which is reported to have exceptional trypanocidal effect on animals infected with both human trypanosomes is “Bayer 205.” Dogs infected with the dourine parasite and showing oedema and eye symptoms have been cured by the injection of the drug intravenously. A dose of 0.5 mg. causes disappearance of parasites in mice. It is stated that the drug produces a protection against reinfection which lasts for months. ”

“ Robust approaches exist for the isolation of human monoclonal antibodies that are elicited following virus infection. Using human PBMCs as a source of memory B cells, we created a panel of human mAbs directed against GII.4 strains and compared the reactivity of these mAbs to a panel of time-ordered GII.4 VLPs using EIAs and surrogate neutralization assays. We identified one novel, broadly cross reactive antibody that differentially blocks GII.4.1987 through 2009 VLP interactions with carbohydrate ligands, a potential immunotherapeutic for the treatment of acute or chronic GII.4 disease. ”

“ In the treatment of trypanosomiasis, concurrently with the use of drugs, every effort should be made to keep the patient in good general health. Rest, warmth, and residence in a cool and healthy climate, the systematic use of quinine for any concurrent malarial infection, and the avoidance of fatigue and everything that might depress, should be insisted on. ”

“ Sometimes none can be found; rarely are they abundant. In the same case they are sometimes present, sometimes absent. Centrifuging the blood is not of much assistance. Dutton and Todd have emphasized the value of lymphatic-gland puncture and examination of the aspirated lymph, particularly in the earlier stages of the disease when the glands are soft and before they have become sclerosed; then the trypanosomes are fairly abundant in the lymph. An ordinary hypodermic syringe suffices to aspirate a sufficiency of lymph. ”

“ Infected cells commonly seen in the lung of fetuses that develop a high titer of antibody for PPV probably represent this stage of replication (see Fig. 17.8C) . Affected cells subsequently round up, become pyknotic, and disintegrate with release of virus and viral antigen (Fig. 17.2B) . Other cells in the culture that are not at the appropriate stage to support viral replication continue to phagocytize and accumulate viral antigen in their cytoplasm (Fig. 17.2C) . ”

“ In experimental rats it has been found possible to transmit infection to other rats through the unbroken skin by rubbing on cultures of this trypanosome.
It is generally held that T. lewisi is non-pathogenic. Certainly, infected rats usually exhibit a remarkable tolerance towards this parasite, but occasionally they do sicken and die.
The fact that the rat is susceptible to laboratory inoculation with the trypanosomes of man and cattle indicates the possibility of finding other species of trypanosomes in the blood of wild rats. ”

“ Kudicke, however, in similar experiments did not succeed in causing re-acquisition by transplantation.
By the action of various drugs and anti-bodies races of trypanosomes resistant to those substances have been obtained. These breed true, at least when kept in the same species of animal in which the resistance was acquired. As to whether change of virulence is produced by passage through certain animals or not, there is as yet no general agreement. ”

“ His work on HIV in Africa highlighted more newly infected HIV-patients with resistant virus [ [16] ] than had been estimated by the WHO. It is a pity that Axel’s excursion into the field of pathogenic retroviruses came so late in his career, although he had been seduced to working on other human pathogens in the course of more clinical studies (HIV-1, parvovirus, Epstein-Barr virus, norovirus, astrovirus, adenovirus, bocavirus, chikungunya virus) .
For many working under his guidance, Axel was a great mentor and a friend beyond their time in his laboratory. ”

“ Here we have expanded these observations using human anti-GII.4 mAbs isolated from a healthy adult donor, who has likely experienced multiple norovirus infections throughout his/her lifetime. The identification of highly significant, varying antigenic epitopes that influence VLP-carbohydrate ligand interaction provides important new insights into vaccine design and the development of therapeutics that target norovirus virions. ”