Unexpectedly higher levels of anti-orthopoxvirus neutralizing antibodies are observed among gay men than general adult population.

BACKGROUND: The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may profoundly impact the transmission of monkeypox virus (MPXV), however the current-day prevalence of antibodies against MPXV among gay men is not well characterized. METHODS: A cohort of gay men (n = 326) and a cohort of the general adult population (n = 295) were enrolled in this study. Binding antibodies responses against MPXV/vaccinia and neutralizing antibody responses against vaccinia virus (Tiantan strain) were measured. The antibody responses of these two cohorts were then compared, as well as the responses of individuals born before and in/after 1981 (when the smallpox vaccination ceased in China). Finally, the correlation between the anti-MPXV antibody responses and the anti-vaccinia antibody responses, and the associations between preexisting anti-orthopoxvirus antibody responses and the diagnosed sexually transmitted infections (STIs) in the MSM cohort were analyzed separately. RESULTS: Our data showed that binding antibodies against MPXV H3, A29, A35, E8, B6, M1 proteins and vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the prevalence of anti-vaccinia binding antibodies was significantly higher among individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the positive rates of binding antibody responses against MPXV H3, A29, A35, E8 and M1 proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the positive rates of anti-MPXV B6 and anti-vaccinia neutralizing antibody responses were significantly higher among these individuals compared to those of age-matched participants in the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-MPXV antibody responses were associated with the anti-vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. The positive rates of both the binding and the neutralizing antibody responses were comparable between individuals with and without diagnosed STIs in the MSM cohort. CONCLUSIONS: Anti-MPXV and anti-vaccinia antibodies could be readily detected in an MSM cohort and a general population cohort. And a higher level of anti-vaccinia neutralizing antibody responses was observed among individuals who did not get vaccinated against smallpox in the MSM cohort compared to age-matched individuals in the general population cohort.

Regulation of Hepatocellular Cholesterol Metabolism By Lactobacillus Paracasei BY2 and Its Embedding Delivery.

In this study, five strains of lactic acid bacteria (LAB) with excellent cholesterol-lowering ability were screened from fermented foods. The gastrointestinal stress resistance, intestinal adhesion, and bacteriostasis abilities were evaluated to obtain the best LAB. And then, high-cholesterol HepG2 cell model was further prepared to explore the cholesterol-lowering mechanism of the LAB. Finally, pH-sensitive hydrogel prepared by Millettia speciosa Champ. carboxymethyl cellulose and Millettia speciosa Champ. cellulose was first applied to the microencapsulation of LAB. As a result, Lactobacillus paracasei BY2 (LP-BY2) exhibited higher cholesterol-lowering activity, intestinal adhesion, and bacteriostasis abilities compared with other LAB. Furthermore, it was found that LP-BY2 could reduce the cholesterol level by regulating the expression of key genes that involved in cholesterol synthesis (HMGCR and SREBP-2), uptake (LDLR), and outflow (LXR-α, ABCA1, ABCG5, ABCG8, and CYP7A1) in liver. At the same time, microencapsulation significantly enhanced the survival rate and cholesterol-lowering ability of LP-BY2 after gastrointestinal digestion. This study will provide an available reference for the application of Lactobacillus in prevention and treatment of hypercholesterolemia.

Analysis of putative N-linked glycosylation sites and variable region of envelope HIV-1 CRF07_BC recombinant in intravenous drug users in Xinjiang Autonomous Region, China.

To investigate more closely the determinants of transmission and escape in HIV-1 internal proteins, we analyzed the characterization of putative N-linked glycosylation sites (PNGSs) and the variable loop of CRF07_BC recombinant human immunodeficiency virus type 1 (HIV-1), isolated from intravenous drug users (IDUs). We studied the characterization of PNGSs and the variable loop in the C1-C5 and V1-V4 regions of the HIV-1 env gene in 12 intravenous drug users (IDUs) who were divided into two groups according to the length of infection time. In addition, two IDUs were longitudinally monitored from the time of seroconversion for 1.5 and 2.5 years. The longitudinal characterization within the individuals on PNGSs and the variable loop in the C1-C5 and V1-V4 region were also observed. Based on the above analysis, we found that PNGSs and the variable loop appeared to increase over time within IDU transmission of CRF07_BC recombinant HIV-1. We argue that limited PNGSs and the length of variable loops may be involved in selective transmission and escape.

A molecular epidemiological study targeting the glycoprotein gene of rabies virus isolates from China.

A group of 31 rabies viruses (RABVs), recovered primarily from dogs, one deer and one human case, were collected from various areas in China between 1989 and 2006. Complete G gene sequences determined for these isolates indicated identities of nucleotide and amino acid sequences of >or=87% and 93.8%, respectively. Phylogenetic analysis of these and some additional Chinese isolates clearly supported the placement of all Chinese viruses in Lyssavirus genotype 1 and divided all Chinese isolates between four distinct groups (I-IV). Several variants identified within the most commonly encountered group I were distributed according to their geographical origins. A comparison of representative Chinese viruses with other isolates retrieved world-wide indicated a close evolutionary relationship between China group I and II viruses and those of Indonesia while China group III viruses formed an outlying branch to variants from Malaysia and Thailand. China group IV viruses were closely related to several vaccine strains. The predicted glycoprotein sequences of these RABVs variants are presented and discussed with respect to the utility of the anti-rabies biologicals currently employed in China.

Genetic and temporal dynamics of human immunodeficiency virus type 1 CRF07_BC in Xinjiang, China.

To explore the temporal genetic variation of human immunodeficiency virus type 1 CRF07_BC and reconstruct its epidemic in Xinjiang, China, we studied 216 C2-V4 fragments of env genes sampled from 1996 to 2008. Phylogenetic analysis indicates that the viruses prevailing in Xinjiang form a large monophyletic cluster and may have originated from a common ancestor. The epidemic in Xinjiang was probably established around 1995 (95% confidence interval, 1994-1996). We noted an increased diversity of CRF07_BC over time, with a rapid evolutionary rate we estimated to be 8.3x10(-3) substitutions per site per year in the env gene. After 5-6 years of the epidemic (1997-2002), the transmission rate of CRF07_BC in Xinjiang slowed down, although CRF07_BC infection remained at a high prevalence.

Dynamic analysis of genetic diversity of gag and env regions of HIV-1 CRF07_BC recombinant in intravenous drug users in Xinjiang Uvghur Autonomous Region, China.

The aim of this study was to investigate the genetic variation of HIV-1 CRF07_BC, the most prevalent circulating strain in intravenous drug users (IDUs) in China. We studied the diversity in the C2-V5 region of the HIV-1 env gene and in the p17-p24 region of the HIV-1 gag gene from the same samples in 12 IDUs who were divided into two groups according to the length of infection time. Two IDUs were longitudinally monitored from the time of seroconversion for 2-2.5 years. The viral divergence from the founder strain and the viral population diversity between sequential time points were analyzed in two men. The data show that the divergence of the env gene is higher than that of gag in general, while the diversity of the gag gene is sometimes higher than that of env during the course of HIV evolution. In addition, env and gag gene diversity increased over time. The observed patterns and associations may enhance our understanding of HIV-1 evolution.

[Dynamic variation of HIV-1 CRF07_BC env gene in early HIV-1 infection].

OBJECTIVE: To understand the evolution of HIV-1 CRF07_BC envelope, we performed a longitudinal study on two patients during their early HIV-1 infection. METHODS: RNA was extracted from the plasma of the individuals and the C2-C5 fragments of the gp120 gene of HIV-1 were amplified by RT-PCR. Purified DNA segments were inserted into T easy vector and transformed into E. coli Top 10 competent cells. Positive clones were identified by blue-white screening, confirmed by PCR and sequenced by ABI 3700. RESULTS: The samples were collected from the patients every 6 months from seroconversion time. The genetic diversity and divergence in env gene showed consistent increases over time. Our sequence analysis also revealed obvious non-synonymous change in env C1, C3 and V4 regions among these samples. CONCLUSION: The results support the concept that the consistent pattern of viral evolution existed during early phase of HIV-1 infection. C1, C3 and V4 region of env gene may be mainly immunological target during AIDS progression.

[Subtype and sequence analysis of gag and env genes among HIV-1 strains circulating in Beijing residents during 2006].

OBJECTIVE: To investigate the subtype distribution and the prevalence of sequence characteristics of HIV-1 strains in Beijing residents during 2006 and to analyze the relationship between distribution of HIV-1 subtypes and transmission routines. METHODS: Blood samples from 32 new confirmed HIV-1 infected individuals from Beijing residents in 2006 and separated plasma specimens were collected. RNAs were extracted and the gag and env gene were amplified by RT-PCR and nest-PCR. PCR products were sequenced directly and phylogenetic analyses of gag and env gene were performed using the MEGA2 software. RESULTS: Among 32 HIV-1 plasma samples, 22 gag and 4 env gene fragments were amplified and analyzed. Five HIV-1 subtypes or circulating recombinant forms(CRFs) of HIV-1 including Thai B (2 strains), B (9 strains), C (2 strains), CRF07_BC (5 strains), CRF01 AE (4 strains) were identified being circulated in Beijing. The gene divergences of gag gene inside the subtypes were 6.6%, 4.3%, 6.8%, 4.9% and 3.0% in subtype B, Thai B, C, CRF01_AE and CRF07_BC respectively. Subtypes B were predominant in Beijing, accounted for 40.9% among 22 samples. CONCLUSION: Five HIV-1 subtypes were identified in Beijing and the surveillance of HIV-1 gene variation should be paid more attention to.