The Evolution of Resistance to Simian Immunodeficiency Virus (SIV): A Review

Examining how pathogens cross species boundaries, spread within species, and persist within their hosts is an essential part of understanding the factors that underpin the evolution of virulence and host resistance. Here, we review current knowledge about the genetic diversity, molecular epidemiology, prevalence, and pathogenicity of simian immunodeficiency viruses (SIVs). SIVs have crossed species boundaries from simian hosts to humans on at least 12 separate occasions, one of which led to the global HIV–AIDS crisis. Though SIVs infect a wide range of primates, scientists have only recently begun to describe the natural history of SIV infection in their natural hosts. Several new studies reveal how both viral and host factors are responsible for the transmission to, and adaptation in, new hosts. These studies also suggest that the spread of the virus may be affected by host-specific traits, including social structure, mating system and demographic history. These studies challenge the traditional view that SIV is relatively benign in its natural host, and instead suggest that a highly dynamic relationship exists between SIV and its simian hosts.     

Functional mapping of MHC class II polymorphic residues. The alpha-chain controls the specificity for binding an Ad-versus an A k-restricted peptide and the beta-chain region 65-67 controls T cell recognition but not peptide binding.

MHC proteins are polymorphic cell surface glycoproteins involved in the binding of peptide Ag and their presentation to T lymphocytes. The polymorphic amino acids of MHC proteins are primarily located in the N-terminal domains and are thought to influence T cell recognition both by influencing the binding of peptide Ag and by direct contact with the T cell receptor. In order to determine the relative importance of individual polymorphic amino acids in Ag presentation, a number of groups have taken the approach of interchanging polymorphic amino acids between different alleles of MHC protein in an attempt to define which of the polymorphisms influence peptide binding and which influence T cell recognition by direct contact with the TCR. The peptide OVA323-339 has been previously shown to bind to the MHC class II protein Ad and to have a much lower affinity for Ak, whereas the peptide hen egg lysozyme 46-61 binds well to Ak and poorly to Ad. In the present report, we have analyzed the ability of purified wild-type MHC class II proteins as well as the ability of three different hybrid molecules between Ad and Ak to bind and present these peptides. We find that the alpha-chain of the MHC class II protein plays a critical role in the binding of HEL46-61 and confers the specificity for binding OVA323-339, regardless of which beta-chain is present. We also find that the beta-chain region 65-67 does not control the specificity of peptide binding to the MHC protein, but is important in T cell responses to preformed MHC-peptide complexes, suggesting a role for this region in contacting the TCR.     

Translocation(X;Y)(p22.33;p11.2) in XX males: Etiology of male phenotype

Summary Analysis of G-banded prometaphase chromosomes from three XX males revealed extra bands on the distal end of one X short arm. These bands were similar both in size and staining properties to the distal Y short arm of their fathers (in the two cases examined) and also to other chromosomally normal males. The extra material on the abnormal X chromosomes was not C-or G-11 positive in the two cases examined, suggesting that the proximal Y long arm was not present.Previous karyotype-phenotype correlations with structurally altered Y chromosomes provided evidence for localization of male determinants on the Y short arm. The present findings in XX males provide support for more precise localization, to bands p11.2pter of Y short arm.     

Management of traumatic intracranial haematoma.

Deciding which head-injured patients should be transferred to a neurosurgical unit can be difficult. Traditional criteria emphasise the development of deteriorating responsiveness but lead to delayed diagnosis and to avoidable mortality and morbidity. To discover if a more liberal admission policy improved results a study was conducted analysing data collected prospectively from 683 patients who had a traumatic intracranial haematoma evacuated in the Glasgow neurosurgical unit between 1974 and 1980. In the first four years, before the change in policy, mortality was 38% but decreased to 29% afterwards. This reflected a reduction in the proportion of patients who talked after injury but who deteriorated into coma before operation--that is, 31% before the change in policy, 16% afterwards. If the potential benefits of CT scanning in the management of head injuries are to be realised patients must be scanned sooner than in the past. This will usually mean that more patients should go to a neurosurgical unit and that simple criteria for transfer should be established.     

Adjusting for regression effect in uncontrolled studies

When clinical studies require enrolled patients to have abnormal assays, the natural tendency of repeat measurements to regress toward the mean can lead to a false assessment of effectiveness of therapy. We propose a method to more accurately estimate the true effect of therapy by adjusting for a component of improvement that can be attributed to regression effect. The model we use allows for a combination of additive and/or multiplicative effects of the therapy.     

Salmonella enterica infections in market swine with and without transport and holding

The objective of this study was to compare, by using identical sample types, the Salmonella enterica prevalences and serovar diversities between pigs necropsied on the farm and those necropsied at the abattoir after transport and holding. We necropsied 567 market weight pigs (>70 kg) from six herds. Pigs were alternately assigned to be necropsied on the farm or at the abattoir. One-half of the group was sent in clean, disinfected trailers to slaughter at a commercial abattoir. After transport (mean distance, 169 km) and 2 to 3 h of holding in antemortem pens, these pigs were necropsied. The 50 pigs remaining on the farm were necropsied the following day. The same sample types and amounts were collected for S. enterica culture at both locations. Results show a sevenfold-higher (P < 0.001) S. enterica isolation rate from pigs necropsied at the abattoir (39.9%; 114 of 286) than from those necropsied on the farm (5.3%; 15 of 281). This difference was also observed for each individual herd. All sample types showed a significantly higher prevalence when comparing abattoir to on-farm collection, respectively: lymph nodes, 9.15 versus 3.6%; cecal contents, 13.6 versus 1.8%; 1 g of fecal matter, 25.2 versus 0.7%. Recovery of additional serovars at the abattoir suggests the pigs are receiving S. enterica from extra-farm sources. This study demonstrates that rapid infection during transport, and particularly during holding, is a major reason for increased S. enterica prevalence in swine. This finding identifies the holding pen as an important S. enterica control point in the pork production chain.