Live-Attenuated Lentivirus Immunization Modulates Innate Immunity and Inflammation while Protecting Rhesus Macaques from Vaginal Simian Immunodeficiency Virus Challenge

Immunization with attenuated lentiviruses is the only reliable method of protecting rhesus macaques (RM) from vaginal challenge with pathogenic simian immunodeficiency virus (SIV). CD8(+) lymphocyte depletion prior to SIVmac239 vaginal challenge demonstrated that a modest, Gag-specific CD8(+) T cell response induced by immunization with simian-human immunodeficiency virus 89.6 (SHIV89.6) protects RM. Although CD8(+) T cells are required for protection, there is no anamnestic expansion of SIV-specific CD8(+) T cells in any tissues except the vagina after challenge. Further, SHIV immunization increased the number of viral target cells in the vagina and cervix, suggesting that the ratio of target cells to antiviral CD8(+) T cells was not a determinant of protection. We hypothesized that persistent replication of the attenuated vaccine virus modulates inflammatory responses and limits T cell activation and expansion by inducing immunoregulatory T cell populations. We found that attenuated SHIV infection decreased the number of circulating plasmacytoid dendritic cells, suppressed T cell activation, decreased mRNA levels of proinflammatory mediators, and increased mRNA levels of immunoregulatory molecules. Three days after SIV vaginal challenge, SHIV-immunized RM had significantly more T regulatory cells in the vagina than the unimmunized RM. By day 14 postchallenge, immune activation and inflammation were characteristic of unimmunized RM but were minimal in SHIV-immunized RM. Thus, a modest vaccine-induced CD8(+) T cell response in the context of immunoregulatory suppression of T cell activation may protect against vaginal HIV transmission.     

Experimental lead poisoning in turkey vultures (Cathartes aura)

Lead-induced mortality appears to have been a major factor in the decline of the California condor (Gymnogyps californianus). We orally dosed turkey vultures (Cathartes aura) with BB-sized lead shot from January 1988 through July 1988 to determine physiologic response (delta-aminolevulinic acid dehydratase inhibition, erythrocyte protoporphyrin levels, anemia), diagnostic tissue lead concentrations (blood, liver, and kidney), and comparative sensitivity of this species. Two turkey vultures died and two became so intoxicated they were euthanized. Overall, responses of measured parameters were comparable to other species exposed to lead although there was considerable individual variation. Survival time (143-211 days), even with the large numbers of shot and constant redosing, was much longer than reported for other species of birds, suggesting considerable tolerance by turkey vultures to the deleterious effects of lead ingestion. Based on these observations, turkey vultures appear to be poor models for assessing the risk of lead poisoning to California condors or predicting their physiologic response.     

Optimizing use of codling moth granulovirus: effects of application rate and spraying frequency on control of codling moth larvae in Pacific Northwest apple orchards

New formulations of the codling moth, Cydia pomonella (L.), granulovirus (CpGV) [family Baculoviridae, genus Granulovirus] are commercially available in North America. In field tests on apple (Malus sp. 'Delicious'), we compared different application strategies for CpGV (Cyd-X, Certis USA, Clovis, CA) used in full-season programs against high pest populations. In replicated single tree plots, three rates (0.073, 0.219, and 0.438 liter ha(-1)) and application intervals (7, 10, and 14 d) killed 81-99% of larvae in fruit and reduced the number of mature larvae recovered in tree bands by 54-98%. Although the proportion of deep entries declined by 77-98%, the amount of fruit injury was not reduced compared with controls. There was a statistical trend between increasing dosage and spray frequency intervals and virus effectiveness, but no interaction between these factors. In a commercial orchard, we assessed a standard (0.219 liter ha(-1)) and two reduced rates of the virus (0.146 and 0.073 liter ha(-1)) applied in a weekly spray program in replicated 0.2-ha blocks. In the first generation, fruit injury was reduced in virus-treated compared with three untreated blocks although the decrease was only significant at the standard rate. Mortality rates of larvae (in fruit) were > or =90%, dose dependent, and comparable with rates observed from individual trees sprayed with equivalent treatments in the previous study. Rates of larval mortality declined at all dosages (81-85%) in the first part of the second generation. Most damage and proportionally less mortality occurred in the upper canopy. High pest pressures and untreated blocks contributed to significant damage and the study was terminated early. These data suggest virus programs can be tailored according to the localized pest pressure, but it may not prevent economic damage in high-pressure situations.     

Memory B cells and CD8⁺ lymphocytes do not control seasonal influenza A virus replication after homologous re-challenge of rhesus macaques

This study sought to define the role of memory lymphocytes in the protection from homologous influenza A virus re-challenge in rhesus macaques. Depleting monoclonal antibodies (mAb) were administered to the animals prior to their second experimental inoculation with a human seasonal influenza A virus strain. Treatment with either anti-CD8α or anti-CD20 mAbs prior to re-challenge had minimal effect on influenza A virus replication. Thus, in non-human primates with pre-existing anti-influenza A antibodies, memory B cells and CD8α⁺ T cells do not contribute to the control of virus replication after re-challenge with a homologous strain of influenza A virus.