Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection

Decreased heat stability and increased chaperone requirement of modified human βB1-crystallins

Purpose: To determine how deamidation and partial loss of the N- and C-terminal extensions alter the heat stability of βB1-crystallin. Methods: Human lens βB1, a deamidated βB1, Q204E, and αA-crystallins were expressed. Truncated βB1 was generated by proteolytic removal of part of its terminal extensions. The aggregation and precipitation of these proteins due to heating was monitored by circular dichroism and light scattering. The effect of heat on the stability of both monomers and oligomers was investigated. The flexibility of the extensions in wild type and deamidated βB1 was assessed by 1H NMR spectroscopy. Results: With heat, deamidated βB1 precipitated more readily than wild type βB1. Similar effects were obtained for either monomers or oligomers. Flexibility of the N-terminal extension in deamidated βB1 was significantly reduced compared to the wild type protein. Truncation of the extensions further increased the rate of heat-induced precipitation of deamidated βB1. The presence of the molecular chaperone, αA-crystallin, prevented precipitation of modified βB1s. More αA was needed to chaperone the truncated and deamidated βB1 than deamidated βB1 or truncated βB1. Conclusions: Deamidation and truncation of βB1 led to destabilization of the protein and decreased stability to heat. Decreased stability of lens crystallins may contribute to their insolubilization and cataract formation

A retrospective multicenter study on the use of locking compression plates for scapulohumeral arthrodesis in small equids

Objective: To report on technical aspects and outcomes after scapulohumeral arthrodesis (SHA) with a locking compression plate (LCP) in small equids. Study design: Retrospective multicenter case series. Animals: Client-owned Shetland Ponies, Miniature Shetlands, and American Miniature Horses (n = 15). Methods: Inclusion criteria were completed SHA with an LCP to treat scapulohumeral osteoarthritis/subluxation and availability of postoperative radiographs. Contributing surgeons completed a questionnaire to collect data. All radiographs were reviewed for this study. Follow-up information was obtained via re-admission to the hospital or telephone interview of the referring veterinarian or owner. Outcome was subjectively scored as excellent, good, moderate, or poor based on lameness and function. Results: Sixteen SHAs were performed in 15 equids (body weight 65-145 kg) by nine different surgeons. A narrow 4.5/5.0 mm LCP (7-16 holes) was used in 14 of the 16 SHAs. Follow-up was collected 2.5 years after surgery (median; range: 9 weeks to 10 years). Major complications related to the SHAs were noted in 4 of the 13 horses alive long term, consisting of implant failure (n = 1), surgical site infection (n = 2), and scapular fracture (n = 1). The outcome was graded as excellent in 4, good in 5, and moderate in 4 horses. Two ponies were euthanized because scapulohumeral osteoarthritis and subluxation developed in the contralateral limb. Conclusion: Although major complications occurred in about one-third of ponies, SHA with LCP led to long-term survival with good function in most ponies. Clinical significance: SHA with an LCP offers a high chance for good long-term outcome in small equids although contralateral disease may affect outcome