ABSTRACT
The membrane-associated RING-CH (MARCH) family of proteins are members of the E3 ubiquitin ligase family and are essential for a variety of biological functions. Currently, MARCH proteins are discovered to execute antiviral functions by directly triggering viral protein degradation or blocking the furin cleavage of viral class I fusion proteins. Here, we report a novel antiviral mechanism of MARCH1 and MARCH2 (MARCH1/2) in the replication of Pseudorabies virus (PRV), a member of the Herpesviridae family. We discovered MARCH1/2 restrict PRV replication at the cell-to-cell fusion step. Furthermore, MARCH1/2 block gB cleavage, and this is dependent on their E3 ligase activity. Interestingly, the blocking of gB cleavage by MARCH1/2 does not contribute to their antiviral activity in vitro. We discovered that MARCH1/2 are associated with the cell-to-cell fusion complex of gB, gD, gH, and gL and trap these viral proteins in the trans-Golgi network (TGN) rather than degrading them. Overall, we conclude that MARCH1/2 inhibit PRV by trapping the viral cell-to-cell fusion complex in TGN.
Subject(s)
Herpesvirus 1, Suid , Ubiquitin-Protein Ligases , Virus Replication , trans-Golgi Network , Herpesvirus 1, Suid/physiology , Animals , trans-Golgi Network/virology , trans-Golgi Network/metabolism , Ubiquitin-Protein Ligases/metabolism , Cell Fusion , Swine , Cell Line , Humans , Viral Proteins/metabolism , Viral Proteins/genetics , HEK293 Cells , Pseudorabies/virologyABSTRACT
Objective: To find out the link between periodontitis and cardiovascular disease while avoiding chronic infections that lead to heart diseases. METHODS: The case-control study was conducted at a tertiary care hospital in Lahore, Pakistan, from October 5, 2017, to January 5, 2018, and comprised patients of cardiovascular disease and healthy controls. Data was collected using questionnaire- based interviews. Data was analyzed using SPSS 20. RESULTS: Of the 146 subjects, 73(50%) each were cases and controls. Among the cases, 48(65.75%) had periodontitis, while 25(34.25%) were free from any history or sign of periodontal infections compared to 16(21.91%) controls who had periodontitis and 57(78.08%) who did not have it (p<0.001). Conclusion: There was a strong association between periodontitis and cardiovascular disease.
Subject(s)
Cardiovascular Diseases , Periodontitis , Cardiovascular Diseases/epidemiology , Case-Control Studies , Humans , Pakistan/epidemiology , Periodontitis/epidemiology , Risk FactorsABSTRACT
BACKGROUND: Live poultry retail stalls (LPRSs) are believed to be the source of human infection with avian influenza viruses (AIVs); however, little is known about epidemiology of these viruses in LPRSs of Pakistan. OBJECTIVES: The current study was conducted to estimate the virological and serological prevalence of AIVs in humans and poultry and associated risk factors among seropositive butchers. METHODS: A field survey of LPRSs of Chakwal District was conducted between December 2015 and March 2016. In total, 322 samples (sera = 161 and throat swab = 161) from butchers and 130 pooled oropharyngeal swabs and 100 sera from birds were collected. Baseline sera (n = 100) from general population were also tested. Data were collected by structured questionnaires. Sera were tested by hemagglutination inhibition (HI) test further confirmed by micro-neutralization test (MN). Swabs were processed by real-time RT-PCR. Logistic regression analyses were conducted to identify risk factors. RESULTS: In butchers, 15.5% sera were positive for antibodies against H9 virus using a cutoff of ≥40 in HI titer; 6% sera from general population were positive for H9. Seroprevalence in poultry was 89%, and only 2.30% swabs were positive for H9. Presence of another LPRS nearby and the number of cages in the stall were risk factors (OR > 1) for H9 seroprevalence in butchers. CONCLUSIONS: This study provides evidence of co-circulation of H9 virus in poultry and exposure of butchers in the LPRSs, which poses a continued threat to public health. We suggest regular surveillance of AIVs in occupationally exposed butchers and birds in LPRSs.