Animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) are still lacking. In this issue, acute pneumonia and severe lung injuries were successfully induced in C57BL/6 mice by the hepatic and neuronal tropic murine coronavirus A-59 (MHV-A59) via intranasal infection. Pathological changes of viral infection were closely monitored, and innate immune responses were studied. The cover image illustrates hemorrhages in the small blood vessels of the mouse lung infected with 1.5 x 105 PFU of MHV-A59 at day 5 post infection. See page 393–402 by Zhangsheng Yang et al. for details.
Lucy Zhu and Hua Zhu. Ocular herpes: the pathophysiology, management and treatment of herpetic eye diseases[J]. Virologica Sinica, 2014, 29(6): 327-342. doi: 10.1007/s12250-014-3539-2.
Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and signifi cant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.
Lilith Torres and Qiyi Tang. Immediate-Early (IE) gene regulation of cytomegalovirus: IE1-and pp71-mediated viral strategies against cellular defenses[J]. Virologica Sinica, 2014, 29(6): 343-352. doi: 10.1007/s12250-014-3532-9.
Three crucial hurdles hinder studies on human cytomegalovirus (HCMV): strict species specifi city, differences between in vivo and in vitro infection, and the complexity of gene regulation. Ever since the sequencing of the whole genome was fi rst accomplished, functional studies on individual genes have been the mainstream in the CMV fi eld. Gene regulation has therefore been elucidated in a more detailed fashion. However, viral gene regulation is largely controlled by both cellular and viral components. In other words, viral gene expression is determined by the virus-host interaction. Generally, cells respond to viral infection in a defensive pattern; at the same time, viruses try to counteract the cellular defense or else hide in the host (latency). Viruses evolve effective strategies against cellular defense in order to achieve replicative success. Whether or not they are successful, cellular defenses remain in the whole viral replication cycle: entry, immediate- early (IE) gene expression, early gene expression, DNA replication, late gene expression, and viral egress. Many viral strategies against cellular defense, and which occur in the immediate-early time of viral infection, have been documented. In this review, we will summarize the documented biological functions of IE1 and pp71 proteins, especially with regard to how they counteract cellular intrinsic defenses.
Jianchun Wei, Hui Chen and Jing An. Recent progress in dengue vaccine development[J]. Virologica Sinica, 2014, 29(6): 353-363. doi: 10.1007/s12250-014-3542-7.
Dengue virus (DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, signifi cant progress has been made. This review summarizes candidate DENV vaccines from recent investigations.
Osamah Barasheed, Harunor Rashid, Mohammad Alfelali, Mohamed Tashani, Mohammad Azeem, Hamid Bokhary, Nadeen Kalantan, Jamil Samkari, Leon Heron, Jen Kok, Janette Taylor, Haitham El Bashir, Ziad A. Memish, Elizabeth Haworth, Edward C. Holmes, Dominic E Dwyer, Atif Asghar, Robert Booy and on behalf of the Hajj Research Team. Viral respiratory infections among Hajj pilgrims in 2013[J]. Virologica Sinica, 2014, 29(6): 364-371. doi: 10.1007/s12250-014-3507-x.
Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the ‘Hajj’ which is the world's the largest mass gathering. Transmission of MERS-CoV at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses (ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the fi rst day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038 (11%) pilgrims. Their mean age was 35 years, 49 (44%) were male and 35 (31%) had received the influenza vaccine pre-Hajj. Forty two (38%) pilgrims had laboratory-confi rmed viral infections; 28 (25%) rhinovirus, 5 (4%) influenza A, 2 (2%) adenovirus, 2 (2%) human coronavirus OC43/229E, 2 (2%) parainfluenza virus 3, 1 (1%) parainfluenza virus 1, and 2 (2%) dual infections. No MERS-CoV was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings.
Yi Huang, Youjie Zhu, Mengshi Yang, Zhenqing Zhang, Donglin Song and Zhiming Yuan. Nucleoprotein-based indirect enzyme-linked immunosorbent assay (indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus[J]. Virologica Sinica, 2014, 29(6): 372-380. doi: 10.1007/s12250-014-3512-0.
Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays (ELISAs) were established for the detection of antibodies specifi c to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in anti- Ebola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G (IgG) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specifi city. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.
Chang Li, Wei Jin, Tao Du, Biao Wu, Yalan Liu, Robin J Shattock and Qinxue Hu. Binding of HIV-1 virions to α4β7 expressing cells and impact of antagonizing α4β7 on HIV-1 infection of primary CD4+ T cells[J]. Virologica Sinica, 2014, 29(6): 381-392. doi: 10.1007/s12250-014-3525-8.
HIV-1 envelope glycoprotein is reported to interact with α4β7, an integrin mediating the homing of lymphocytes to gut-associated lymphoid tissue, but the signifi cance of α4β7 in HIV-1 infection remains controversial. Here, using HIV-1 strain BaL, the gp120 of which was previously shown to be capable of interacting with α4β7, we demonstrated that α4β7 can mediate the binding of whole HIV-1 virions to α4β7-expressing transfectants. We further constructed a cell line stably expressing α4β7 and confirmed the α4β7-mediated HIV-1 binding. In primary lymphocytes with activated α4β7 expression, we also observed significant virus binding which can be inhibited by an anti-α4β7 antibody. Moreover, we investigated the impact of antagonizing α4β7 on HIV-1 infection of primary CD4+ T cells. In α4β7-activated CD4+ T cells, both anti-α4β7 antibodies and introduction of shorthairpin RNAs specifically targeting α4β7 resulted in a decreased HIV-1 infection. Our findings indicate that α4β7 may serve as an attachment factor at least for some HIV-1 strains. The established approach provides a promising means for the investigation of other viral strains to understand the potential roles of α4β7 in HIV-1 infection.
Zhangsheng Yang, Jun Du, Gang Chen, Jie Zhao, Xuanming Yang, Lishan Su, Genhong Cheng and Hong Tang. Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice[J]. Virologica Sinica, 2014, 29(6): 393-402. doi: 10.1007/s12250-014-3530-y.
It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59 (MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Infl ammatory leukocyte infi ltrations, hemorrhages and fi brosis of alveolar walls can be observed 2-11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.
Xiaowei Xu, Sulin Ren, Xiaoxiao Chen, Jun Ge, Zhenxing Xu, Hongying Huang, Honglin Sun, Yue Gu, Tong Zhou, Jianqiang Li and Hanmei Xu. Generation of Hepatitis B virus PreS2-S antigen in Hansenula polymorpha[J]. Virologica Sinica, 2014, 29(6): 403-409. doi: 10.1007/s12250-014-3508-9.
Despite the long availability of a traditional prophylactic vaccine containing the HBV surface antigen (HBsAg) and aluminum adjuvant, nearly 10% of the population remains unable to generate an effective immune response. Previous studies have indicated that hepatitis B virus (HBV) PreS2-S is abundant in T/B cell epitopes, which induces a stronger immune response than HBsAg, particularly in terms of cytotoxic T lymphocyte (CTL) reaction. In the current study, the HBV PreS2-S gene encoding an extra 26 amino acids (PreS2 C-terminus) located at the N-terminus of HBsAg was cloned into the pVCH1300 expression vector. PreS2-S expressed in the methylotrophic yeast, Hansenula polymorpha, was produced at a yield of up to 250 mg/L. Subsequent purifi cation steps involved hydrophobic adsorption to colloidal silica, ion-exchange chromatography and density ultracentrifugation. The fi nal product was obtained with a total yield of ~15% and purity of ~99%. In keeping with previous studies, ~22 nm viruslike particles were detected using electron microscopy. The generated PreS2-S antigen will be further studied for effi cacy and safty in animals.