Porcine reproductive and respiratory syndrome (PRRS) consistently elevates the frequency of disease and mortality in young pigs. Many different secondary bacterial diseases occur in PRRS virus (PRRSV)-infected pigs. However, to date, establishing a reproducible experimental model of PRRSV infection in weaned pigs, with subsequent clinical disease following secondary bacterial challenge, has been difficult. PRRSV is frequently isolated during outbreaks from weak-born piglets affected by secondary bacterial diseases. This study was performed to investigate the potential role of intrauterine PRRSV infection on piglet susceptibility to secondary bacterial infection. PRRSV-free pregnant sows were intranasally infected at 98 days of gestation with PRRSV strain SD 23983. All piglets born to the PRRSV-infected sows were viremic. Piglets were removed from the sows at birth and deprived of colostrum. Piglets from PRRSV-infected and noninfected sows were randomly assigned to Streptococcus suis challenge or control subgroups. At 5 days of age, piglets were challenged intranasally with strain MN 87555 of S. suis type II. Total and differential leukocyte counts were performed on blood samples collected at 3 days of age. The numbers of leukocytes, lymphocytes, and monocytes were significantly reduced in the PRRSV-infected piglets. Lesions were observed in bone marrow, brain, lung, heart, spleen, lymph node, tonsil, and thymus of PRRSV-infected piglets. Thymus/body weight ratios of in utero PRRSVinfected piglets were significantly reduced compared to those of non-PRRSV-infected piglets, and thymic lesions were characterized by severe cortical depletion of thymocytes. Lesions were not observed in piglets born to PRRSV-free sows. Overall, 20 out of 22 piglets in the PRRSV-S. suis dual-infection group died within 1 week after challenge with S. suis (10 of 11 in each of two trials). This contrasts with 1 of 18 piglets in the PRRSVinfection-only group and 5 of 23 piglets in the S. suis-challenge-only group (1 of 12 in trial 1 and 4 of 11 in trial 2). No piglets died in the uninfected control groups. Most of the piglets in the PRRSV-S. suis dual-infection group developed suppurative meningitis. S. suis type II was recovered from their brains and joints. These results indicate that in utero infection by PRRSV makes piglets more susceptible to infection and disease following challenge by S. suis type II. In utero infection by PRRSV may provide a useful model to study the interaction between PRRSV and bacterial coinfections in piglets.

No abstract

Piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV) are born severely immunocompromised. In this article we more closely examine the effects of in utero PRRSV infection on circulating and thymic T cell populations. Numbers of CD4+, CD8+, and dual-positive lymphocytes were quantitated in circulation and in the thymus during the 2 weeks following birth. At birth we found that the number of circulating lymphocytes was suppressed by 60%. Lymphocyte numbers were also suppressed by 42% at day 7, but by day 14 the number of lymphocytes had rebounded and was actually 47% greater than controls. At birth and day 7, a drop in the number of CD4+ cells could partially explain the suppression we observed, while the rebound in total lymphocyte numbers seen at day 14 was due to a nearly fourfold increase in the number of circulating CD8+ cells. As a result, the normal CD4+:CD8+ ratio of between 1.4 and 2.2 for neonatal pigs was reduced to 0.1-0.5. The thymuses of infected piglets were found to be 50% smaller than those of control pigs and were characterized by cortical involution and severe cortical depletion of thymocytes. Analysis of the population of thymocytes revealed that double-positive thymocytes were suppressed to a greater degree than either single positive subpopulation. In addition, we show that the number of thymocytes undergoing apoptosis was increased twofold in piglets infected with PRRSV. Taken together, these results help explain the dramatic immunosuppression observed in neonatal animals infected in utero with PRRSV.

The objective of this paper is to correlate the MRI distribution of cryptococcal meningoencephalitis in HIV-1 infection patients with CD4 T cell count and immune reconstitution effect.A large retrospective cohort study of HIV patients from multi-HIV centers in China was studied to demonstrate the MRI distribution of cryptococcal meningoencephalitis and its correlation with the different immune status.The consecutive clinical and neuroimaging data of 55 HIV-1-infected patients with cryptococcal meningoencephalitis collected at multi-HIV centers in China during the years of 2011 to 2014 was retrospectively analyzed. The enrolled patients were divided into 2 groups based on the distribution of lesions. One group of patients had their lesions at the central brain (group 1, n = 34) and the other group of patients had their lesions at the superficial brain (group 2, n = 21). We explored their MRI characterization of brain. In addition, we also compared their CD4 T cell counts and immune reconstitution effects between the 2 groups based on the imaging findings.No statistical difference was found in terms of age and gender between the 2 groups. The medians of CD4 T cell counts were 11.67 cells/mm3 (3.00–52.00 cells/mm3) in group 1 and 42.00 cells/mm3 (10.00–252.00 cells/mm3) in group 2. Statistical difference of CD4 T cell count was found between the 2 groups (P = 0.023). Thirteen patients in group 1 (13/34) and 12 patients in group 2 (12/21) received highly active antiretroviral treatment (HAART). Patients of group 2 received HAART therapy more frequently than patients of group 1 (P = 0.021).Central and superficial brain lesions detected by MR imaging in HIV-1-infected patients with cryptococcal meningoencephalitis are in correlation with the host immunity and HAART therapy.