RESUMO
The COVID-19 pandemic is caused by the worldwide spread of the RNA virus SARS-CoV-2. Because of its mutational rate, wide geographical distribution, and host response variance this coronavirus is currently evolving into an array of strains with increasing genetic diversity. Most variants apparently have neutral effects for disease spread and symptom severity. However, in the viral spike protein, which is responsible for host cell attachment and invasion, the D614G variant, containing the amino acid substitution D to G in position 614, was suggested to increase viral infection capability. Here we propose a novel method to test the epidemiological impact of emergence of a new variant, by a combination of epidemiological curves (for new cases) and the temporal variation of relative frequencies of the variants through a logistic regression model. We applied our method to temporal distributions of SARS-CoV-2 D614 or G614, in two geographic areas: USA (East Coast versus West Coast) and Europe-Asia (East Countries versus West Countries). Our analysis shows that the D614G prevalence and the growth rates of COVID-19 epidemic data curves are correlated at the early stages and not correlated at the late stages, in both the USA and Europe-Asia scenarios. These results show that logistic models can reveal the potential selective advantage of D614G, which can explain, at least in part, the impact of this variant on COVID-19 epidemiology.
Assuntos
Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , DNA Viral/análise , Feminino , Variação Genética , Protease de HIV/genética , Humanos , Dados de Sequência Molecular , América do Norte , Polimorfismo de Fragmento de Restrição , Porto Rico , Vigilância de Evento Sentinela , Trabalho SexualRESUMO
The genetic variation of the human immunodeficiency virus type 1 (HIV-1) protease gene (prt) permits the classification of HIV-1 strains into five distinct protease subtypes, which follow the gag subtyping patterns. The susceptibilities of non-B-subtype strains to protease inhibitors (PIs) and other antiretroviral drugs remain largely unknown. Subtype F is the main non-B strain contributing to the Brazilian epidemic, accounting for 15 to 20% of these infections. In this work, we report the findings on 81 isolates from PI-naive Brazilian patients collected between 1993 and 1997. In addition, the relevant PI resistance mutations and their phenotypes were determined in vitro for 15 of these patients (B = 9 and F = 6). Among these, the subtype F samples evidenced high sensitivities in vitro to ritonavir and indinavir, with MICs at which 50 and 90% of the isolates are inhibited similar to those of both the Brazilian and the U.S. subtype B isolates. Analysis of the 81 Brazilian prt sequences demonstrated that the subtype F consensus sequence differs from the U.S. and Brazilian subtype B consensus in eight positions (I15V, E35D, M36I, R41K, R57K, Q61N, L63P, and L89M). The frequency of critical PI resistance substitutions (amino acid changes D30N, V82A/F/T, I84V, N88D, and L90M) among Brazilian isolates is very low (mean, 2.5%), and the associated secondary substitutions (amino acid positions 10L, 20K, 36M, 46M, 48G, 54I, 63P, 71A, and 77A) are infrequent. These observations document the relative rarity of resistance to PIs in the treatment of patients infected with HIV-1 subtype F in South America.
Assuntos
Fármacos Anti-HIV/farmacologia , Variação Genética , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , Protease de HIV/genética , HIV-1/efeitos dos fármacos , Indinavir/farmacologia , Saquinavir/farmacologia , Sequência de Aminoácidos , Brasil , DNA Viral/análise , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de AminoácidosRESUMO
This article describes a case of horizontal (heterosexual) and subsequent vertical (mother to infant) transmission of 2 human immunodeficiency viruses type 1 (HIV-1) subtypes. Dual infection in a husband, his wife, and their child was initially detected by use of a restriction fragment length polymorphism assay of the proviral protease in peripheral blood mononuclear cells. The simultaneous presence of highly similar sets of HIV-1 subtypes B and C infecting the 3 family members was confirmed by DNA sequence analysis of pol, gag, and env genes. These data, together with available epidemiologic information, may indicate that the husband's high-risk sexual behavior was the source of dual infections. Because his wife did not report such activities, it was likely that he passed HIV-1 strains to his spouse, who subsequently transmitted them to their child.