Rhesus CMV: an emerging animal model for human CMV

Human CMV is the predominant infectious cause of congenital birth defects and an opportunistic pathogen in immunosuppressed individuals, including AIDS patients. Most individuals are infected early during their life followed by life-long latent infection. During this latent phase, frequent reactivation and antigen production continue to stimulate the immune system. While the immune response is able to control the virus, it is unable to eradicate it. Moreover, super-infection by different CMV strains has been observed despite a strong immune response. Long-term immune stimulation by CMV has also been implicated in immune senescence and chronic conditions such as atherosclerosis. CMVs are highly species-specific and the relatedness of CMV genomes exactly mirrors the relatedness of their hosts. Thus, each CMV species is highly adapted to its respective host species, but is unable to infect other, even closely related hosts. While fascinating from an evolutionary perspective, this host restriction prevents studying HCMV in experimental animals. Exceptions are severely immunocompromised mice, e.g. SCID mice, or SCID/NOD mice, which might allow partial reconstitution of CMV infection in rodents. More practical however, is to study CMVs in their natural host, e.g. murine, rat or guinea pig CMVs. However, while these small animal models have many advantages, such as the availability of inbred animals as well as lower cost, the limited homology of the viral genomes with HCMV limits the functional analysis of homologous gene products. The closest relative to HCMV is chimpanzee CMV (CCMV), but this is not a practical animal model since chimps are a protected species, extremely expensive and of very limited availability. In contrast, rhesus macaques are a more widely used experimental animal species and, while more distant than CCMV, rhesus CMV (RhCMV) contains most of the HCMV gene families thus allowing the study of their role in acute and latent CMV infection. In this review we will discuss the current state of developing RhCMV as a model for HCMV.     

Human herpesvirus 6‐A, 6‐B,and 7 in vitreous fluid samples

Human herpesvirus 6 and 7 (HHV‐6, HHV‐7) have been associated with several neurologic syndromes and have been detected in nervous tissue from healthy persons; however, only two cases of HHV‐6A have been reported to be associated with intraocular inflammatory disease. Vitreous fluid was tested from 101 patients, including 69 samples from patients with ocular inflammation including CMV retinitis, idiopathic retinitis, iritis, and vitritis, for HHV‐6A, HHV‐6B, and HHV‐7 DNA by PCR. HHV‐6A DNA (4,950 copies per ml) was detected in vitreous fluid from one patient with CMV retinitis, HHV‐6B DNA (10,140 copies per ml) was detected in vitreous fluid from one patient with idiopathic ocular inflammation in the absence of CMV DNA, and HHV‐7 was not detected in any of the vitreous samples. HHV‐6A, HHV‐6B, and HHV‐7 DNA are detectable in less than 2% of vitreous samples in patients with ocular inflammation. J. Med. Virol. 82:996–999, 2010. © 2010 Wiley‐Liss, Inc.     

Regulatory function of cytomegalovirus-specific CD4CD27CD28 T cells

CMV infection is characterized by high of frequencies of CD27⁻CD28⁻ T cells. Here we demonstrate that CMV-specific CD4⁺CD27⁻CD28⁻ cells are regulatory T cells (T_R). CD4⁺CD27⁻CD28⁻ cells sorted from CMV-stimulated PBMC of CMV-seropositive donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose-dependent fashion. Compared with the entire CMV-stimulated CD4⁺ T-cell population, higher proportions of CD4⁺CD27⁻CD28⁻ T_R expressed FoxP3, TGFβ, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L. CMV-CD4⁺CD27⁻CD28⁻ T_R expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4⁺CD27⁻CD28⁻ T_R significantly decreased after granzyme B or TGFβ inhibition. The CMV-CD4⁺CD27⁻CD28⁻ T_R of HIV-infected and uninfected donors had similar phenotypes and anti-proliferative potency, but HIV-infected individuals had higher proportions of CMV-CD4⁺CD27⁻CD28⁻ T_R. The CMV-CD4⁺CD27⁻CD28⁻ T_R may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals.     

促红细胞生成素对视网膜色素变性的RCS大鼠的作用

为观察促红细胞生成素对视网膜色素变性的RCS大鼠的作用,探讨其对视网膜变性神经元保护的可能机制。我们把出生后雄性RCS大鼠48只,随机分为给药组和对照组。RCS大鼠给药组从生后5d开始腹腔注射重组人促红细胞生成素(rhEPO),每5d注射一次,剂量为4000IU/kg。RCS大鼠对照组注射生理盐水,剂量同上。HE染色和TUNEL检测观察rhEPO对视网膜色素变性神经元的保护作用。应用免疫组织化学方法检测caspase2蛋白的表达。结果显示:(1)RCS大鼠给药组20d,25d,感光细胞的数目与对照组大鼠相比明显增加(P<0.05);(2)RCS大鼠给药组25dTUNEL检测阳性细胞数目与对照组相比,差异有统计学意义(P<0.05);(3)生后25d到40d,RCS大鼠给药组和对照组在节细胞层和内核层观察到caspase2阳性染色,RCS大鼠给药组在20d和25d内核层caspase2阳性细胞数目多于对照组(P<0.05)。结果提示:在RCS大鼠视网膜变性的早期,rhEPO对神经元起保护作用,可以使感光细胞得到更多存留;rhEPO对视网膜变性神经元的早期保护作用可能是通过抑制凋亡的方式进行的;caspase2蛋白在视网膜的一过性高表达提示其参与了视网膜感光细胞的凋亡过程,rhEPO可减少其早期的表达,对早期变性的神经元发挥保护作用。     

丙种球蛋白治疗新生儿巨细胞病毒肺炎的临床疗效分析

目的探讨丙种球蛋白治疗新生儿巨细胞病毒感染性肺炎的疗效和安全性。方法回顾于2000年7月至2006年3月入院的24例新生儿巨细胞病毒感染性肺炎患儿,随机分为两组进行对照研究,入选患儿常规抗生素治疗,明确病原后予对因治疗,对照组应用更昔洛韦,每次5mg/kg,每12h1次,疗程14d;治疗组用静脉用丙种球蛋白每日400mg/kg,疗程10d。观察项目:①临床指标:住院天数、肺部体征开始消退时间。②实验室指标:血常规、肝功能、HCMV-DNA量的变化。③随访观察:出院后每3个月随访一次,包括临床表现、体征和FQ-PCR测定HCMV-DNA拷贝数。结果静脉用丙种球蛋白治疗组有效率81.8%,治疗组有效率53.8%,两组疗效相近,差异无统计学意义(χ2=2.329,P>0.05),治疗组平均住院日为(23±5.6)d,对照组为(28.6±7)d,差异有统计学意义(t=-2.164,P<0.05)。肺部体征开始消退天数分别为(7.45±1.37)d和(9.58±2.61)d,存在统计学差异(t=-2.415,P<0.05)。对照组有2例因WBC<0.5×109/L,plt<25×109/L,而终止治疗,1例治疗过程中死于呼吸衰竭。结论丙种球蛋白治疗新生儿巨细胞病毒感染性肺炎疗效与更昔洛韦相近,相对于更昔洛韦,在治疗新生儿巨细胞病毒感染性肺炎,特别是合并多种病原体混合感染,静脉用丙种球蛋白具有较好的疗效和安全性。     

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

Retinitis pigmentosa (RP) is a group of retinal dystrophies characterised primarily by rod photoreceptor cell degeneration. Exhibiting great clinical and genetic heterogeneity, RP be inherited as an autosomal dominant (ad) and recessive (ar), X-linked (xl) and digenic disorder. RP25 , a locus for arRP, was mapped to chromosome 6p12.1-q14.1 where several retinal dystrophy loci are located. A gene expressed in the retina, FAM46A , mapped within the RP25 locus, and computational data revealed its involvement in retinal signalling pathways. Therefore, we chose to perform molecular evaluation of this gene as a good candidate in arRP families linked to the RP25 interval. A comprehensive bioinformatic and retinal tissue expression characterisation of FAM46A was performed, together with mutation screening of seven RP25 families.
Herein we present 4 novel sequence variants, of which one is a novel deletion within a low complexity region close to the initiation codon of FAM46A . Furthermore, we have characterised for the first time a coding tandem variation in the Caucasian population.
This study reports on bioinformatic and moleculardata for the FAM46A gene that may give a wider insight into the putative function of this gene and its pathologic relevance to RP25 and other retinal diseases mapping within the 6q chromosomal interval.     

Human mast cells present antigen to autologous CD4+ T cells

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